White House spokesman Larry Speakes, responding to criticism that he had misled the public about the cancerous growth removed from President Reagan's nose, accused two reporters yesterday of "blindly, unjustifiably, recklessly" questioning his credibility.

In a statement read with emotional emphasis at yesterday's morning briefing, Speakes defended his 18-year record as a Washington spokesman, the last 4 1/2 years for Reagan. He said that despite "unnecessarily personal" accusations by Sam Donaldson of ABC News and Helen Thomas of United Press International, his reputation "for being truthful remains."

Hours after he made these comments, Speakes issued another statement that illustrated the problem that has confronted the White House ever since officials, reportedly at the instruction of Nancy Reagan, decided to limit information about the removal of the growth from the president's nose.

The latest statement said that a 1 percent solution of xylocaine, a common painkiller, was used as a local anesthetic when the cancer was removed from Reagan's nose. Last Thursday, Speakes repeatedly denied that an anesthetic had been used. He said yesterday that he had received the information from the physicians who performed the operation.

Speakes said that when a New York Times medical writer told him that a local anesthetic was commonly used in such cases, he went back to the doctors, who told him about the xylocaine. He called it a "standard dermatological procedure for lesions of this kind."

In the statement read at yesterday morning's briefing, Speakes said: "It's not an easy job to serve two masters, the press and the president, but first of all you serve your country. I have done that and I will continue to do so, from this podium . . . . I will tell the truth always."

However, neither Donaldson nor Thomas backed away from statements that Speakes had misled reporters.

Donaldson later tacked a one-page letter on the White House bulletin board, addressing Speakes as "Dear Larry," and praising him for usually doing a good job of "walking that tightrope between presidents and the press." But he repeated the charge he made at a Tuesday briefing that Speakes had lost credibility in dealing with the skin cancer story.

"I believe you knew you were misleading reporters, and through them the public, as to the true nature of the president's malady by (1) withholding pertinent information, (2) issuing a statement last Thursday under the heading of the 'Office of the Press Secretary' obviously crafted to leave the reader with the false impression that the skin swatch had been checked for infection only, and (3) failing to correct that false impression although you were repeatedly given the chance during public questioning to do so," Donaldson's letter said.

Thomas did not issue any statements. But she agreed with Donaldson that Speakes displayed "a lack of candor" during the incident.

"The White House spoke with three voices on this issue," Thomas said. "Speakes is the spokesman and he has a responsibility to get the facts together."

Thomas referred to statements from aides to Nancy Reagan and from White House physician T. Burton Smith denying that a biopsy had been performed or that Reagan's growth was cancerous. Smith told The Associated Press on Thursday, the same day the White House received a preliminary report on the biopsy, that the growth was not cancerous.

The White House physician did not perform the surgery, which was done by a dermatologist whom Speakes has declined to identify.

The growth was removed from Reagan's nose on July 30. Two days later, when the preliminary report went to the White House, Speakes issued a statement saying that the tissue "was submitted for routine studies for infection and it was determined that no further treatment is necessary."

The statement did not mention a biopsy or cancer, and Speakes declined to answer questions. Jennefer Hirshberg, Nancy Reagan's press secretary, said subsequently that neither of the Reagans knew until the weekend at Camp David that a biopsy had been performed or what the results had been. The president disclosed that the growth was cancerous when he met with reporters on Monday.

Donaldson's statement alluded to reports that Speakes in private discussions had opposed the "policy obfuscation" reportedly ordered by Nancy Reagan, but said that was "beside the point" on the credibility issue.

In Speakes' statement to reporters, he pledged to "deal with each of you honestly, truthfully and with professionalism. You have a job to do and we have a job to do, and we will do it with respect for each other."

"Today I'm in the briefing room for the 1,525th time," Speakes said. "That's a lot of water under the bridge. And never once, never once has my honesty been questioned."