Generic versions of prescription drugs, some costing as little as half as much as their brand name counterparts, have been coming on the market in larger numbers.

In the past two years, the patents of more than a dozen top-selling drugs, including Valium, have expired.

But as generic drugs move into the marketplace, brand name drug makers have begun fighting back. Advertisements have sought to to build brand name loyalities and to raise questions about the effectiveness of the generics.

The three-decade-old rivalry has intensified since last year, when Congress passed a major reform bill that speeds up the federal approval process for generics even as it extended the patent life of brand name pharmaceuticals.

Last year, generic sales were about $4 billion, about 18 percent of the total prescription drug market. Sales are expected to jump because the new law freed up more than 100 drugs whose patents had expired but could not easily be copied under the old law's restrictions. And the patents on other big sellers, such as the antibiotic Keflex -- which had sales of $174 million last year -- will expire over the next few years.

The National Council of Senior Citizens estimates that the use of generics could reduce the nation's health care bill by as much as $1 billion over the next 12 years.

Generic use will go up, said Dee Fensterer, director of the Generic Pharmaceutical Industry Assoc., because of the improved image of generic drugs and the drive by government, employers, insurers and consumers to cut medical costs.

By law, generic drugs must contain the same active ingredient, in the same concentration, as the brand name drug. The generic version of a 10 milligram Valium must contain 10 mg of diazepam, the tranquilizer's active ingredient.

Besides price, the only difference between generic and brand name drugs is in the composition of inactive ingredients, such as preservatives, color additives, and starches that bind a pill together. Those differences can affect, for example, how fast a pill dissolves or is taken up in the blood stream.

Based on those variations, the Food and Drug Administration has two main categories of generic drugs.

The larger group, 80 percent of all generics, can be interchanged for the prescribed brand name drug, including Valium, Inderal (for hypertension), Motrin (for arthritis and pain relief), and Darvocet-N100 (for pain relief).

The blood levels of those generics can fluctuate by 20 percent. This difference has little, if any, therapeutic significance, said Marvin Seife, FDA's director of generic drugs.

Such variations are allowed because clinical studies have shown that the concentration of any drug in a person's blood can vary from time to time -- even when the person is taking the exact same formula in the exact same dose.

Some brand name companies have claimed that the variations show that the generics are inferior. Actually, the blood concentrations of brand name drugs fluctuate by the same amount.

The second group of generics are not considered to be therapeutically identical to brand name drugs and cannot be automatically substituted, although they contain the same active ingredients. The physician must prescribe them specifically, just as if they were brand name drugs.

To ensure that a generic is equivalent to a brand name drug, the FDA measures the concentrations of each drug in the blood, said Shrikant Dighe, director of FDA's division that monitors bioequivalence. To do the test, a generic drug is given to about 24 patients for one to four weeks. During this time, blood samples are periodically taken to measure the concentration of drug. Then no drug is given for about a week to clear the body.

Then the brand name drug is given to the same individuals for the same period of time and the blood levels are measured again. Since the same individuals are used, the absorption of both generic and brand name drugs can be compared in the same person.

For some drugs, Dighe says, additional tests are conducted. With antihypertension drugs, blood pressure is measured. With diabetic drugs, blood sugar levels are monitored.

As more generics make their debuts, brand name companies are trying various methods to keep customers loyal. They have argued that they need profits to continue research and development of new drugs. But generic companies and the FDA have balked at some of the tactics used.

For almost the past two years, Sandoz Inc., manufacturer of the antidepressant Mellaril, had been running ads that claimed Mellaril substitutes may produce "unpredictable results" because of ". . . widely varying blood levels."

In a Sept. 5 letter, the FDA warned the company to stop implying that the variations were clinically important. Noting that Mellaril produces similar variations, Peter Rheinstein, director of FDA's office of drug standards, wrote: "Your continued use of misleading promotional material and your activities aimed at discrediting competing Mellaril products without scientific basis are flagrant, repeated and willful violations of the federal, Food, Drug, and Cosmetic Act."

The FDA demanded that Sandoz immediately cancel ads that "convey the deceptive information" and send letters to pharmacists to set the record straight.

"We don't agree with the letter," said Sandoz spokesman Craig Burrell. "We don't like its tone or content."

He said the company is trying "to work things out with FDA." No more of the ads in dispute have been run since FDA's warning, but the company has not sent "Dear Pharmacist" letters, Burrell said.

Hoffmann-LaRoche Inc. took a new tact with Valium. It attempted this year to block federal approval of generic diazepam, asserting that FDA was using the wrong test to judge bioequivalency. It asserted that computerized brain wave tests should be used rather than blood serum levels. The agency rejected that argument because the company failed to present clinical evidence to support its claim.

Hoffman-LaRoche, like other companies, is coming up with new identifying marks for its products. Valium tablets now have a V-shaped hole in the middle. Ayerst Laboratories inscribed an "I" on its tablets of Inderal, an antihypertensive.

Ayerst also has run Inderal ads in medical journals during the past year, which show a doctor saying, "When it comes to cardiovascular medicine, I like to know exactly what my patients are swallowing."

Some companies are also reformulating their products by combining them with other types of drugs and then patenting the combinations, said Marcia Codling, a practicing pharmacist and an analyst at the Arthur D. Little Co. in Boston.

In an "if you can't beat them, join them" move, established brand name companies have begun producing more generics, too.

The Parke-Davis Division of Warner Lambert, for example, now makes generic Valium. Other companies making new generics include Eli Lilly, Lederle Laboratories, and Smith Kline & French.

And some generics producers are conducting their own research to produce new name brand drugs, such as Maxide, a heart drug.

While generics may give consumers a less expensive alternative, they do a pecular thing to the prices of brand name drugs: they drive them up.

"What they can't make up in volume, brand name companies make up in price," said Little's Codling.

So even though generics sell their products for less than the brand name price, does the consumer come out ahead?

Yes, Codling says. "If you have two or three generic competitors, the consumer ultimately benefits."