Dr. William H. Foege, who as an epidemiologist led the successful fight to eradicate smallpox and later presided over the investigations into toxic shock syndrome and Legionnaire's Disease, has resigned as director of the national Centers for Disease Control.

In an April 4 letter to Edward N. Brandt Jr., assistant secretary of the Health and Human Services Department, Foege, 46, said, "After six of the most exciting and professionally satisfying years of my life, I believe it is the right time, with your approval, to shift responsibilities." Foege added that he wanted to stay at the CDC working on international projects and "CDC-academia relationships."

Although Foege had told colleagues when he took the post that he only wanted to serve five years, his resignation caught many subordinates by surprise. "Nobody wanted him to go," said one Health and Human Services official. "It's not because of any problem. It's Foege's choice."

At the time of the announcement, many officials of the Atlanta-based agency were attending a meeting in Bethesda on Acquired Immune Deficiency Syndrome (AIDS), one of the newest and most serious diseases the agency is investigating. Donald Francis, one of the CDC officials at the meeting, said, "It will be difficult to replace someone with his talents. He's a winner. He's more than paid his dues."

Foege is given particular credit by his colleagues in government and in the medical community for his low-key but effective effort to fight massive budget cuts and win congressional approval for increased CDC funding. The Reagan administration budget for fiscal 1983 called for a 23 percent cut in the agency's $283 million budget; the final appropriation provided the CDC with more than a $50 million increase.

Foege, who has worked at the CDC almost his entire professional career after two years in Nigeria as a medical missionary, is best known for helping lead the worldwide effort to eradicate smallpox.

Dr. Donald Henderson, who also led that fight and now serves as dean of the School of Hygiene and Public Health at Johns Hopkins University, said, "He's a splendid person. There aren't many people who have the background and knowledge in international health that Bill Foege has."

Henderson added that he had tried to recruit Foege to join the Hopkins faculty but that Foege resisted, saying he wanted "time to think about what he wants to do."

In addition to the budget fights, Foege's tenure as CDC director was marked by major investigations into the health effects of Agent Orange, the dioxin-based herbicide used in Vietnam, and Reye's syndrome, a fatal disease that most commonly strikes young children.