Forty-three patients with advanced, primarily untreated Hodgkin's disease were treated with a combination of vincristine sulfate, nitrogen mustard (or cyclophosphamide), procarbazine hydrochloride, and prednisone, given in cyclical fashion for 6 months. The limiting toxicity was primarily bone marrow suppression and, although occasionally severe, was generally tolerable. Other toxicity such as alopecia and neurotoxicity were troublesome but reversible. The response rate was superior to that previously reported with the use of single drugs with 35 of 43, or 81% of the patients achieving a complete remission, defined as the complete disappearance of all tumor and return to normal performance status. The duration of these responses after all therapy was discontinued was gratifyingly long, with a median of not less than 29 and not more than 42 months. Seventeen of 35 patients continue free of their disease, and 28 of these 35 are still alive. The median survival of the responding group is greater than 42 months, and life table analysis of the results indicates that of those complete responders at risk for 4 years, 77% remain alive and 47% are continuously free of their disease. The surviving fraction of the entire group at risk 4 years is 63%. It appears that combinations of effective drugs that act by different mechanisms and manifest different toxicities can be used effectively to increase the response rate and probably the survival of patients with sensitive tumors such as Hodgkin's disease.