Retrospective pathological classification of 213 patients with malignant melanoma identified a group at high risk of recurrence (25% developed recurrence in 12 months, 50% by 5 years) after resection for apparent cure. Using these criteria, 70 patients were identified after resection of all apparent disease as being at high risk for recurrent melanoma. They were randomly assigned to one of the three adjuvant treatment arms: chemotherapy with dimethyl triazeno imidazole carboxamide (DTIC), immunotherapy with bacillus Calmette-Guerin (BCG), or combined chemoimmunotherapy. Six of 20 patients receiving DTIC developed recurrence (30%) and four died (20%). Five of 28 patients receiving BCG developed recurrence (18%) and two died (7.5%). There have been no recurrences or deaths in 22 patients receiving combined chemoimmunotherapy. In the prevention of early recurrence, the combined therapy arm was significantly superior to both the immunotherapy arm (p less than 0.05) and the chemotherapy arm (p less than 0.01). In terms of survival, combined therapy also was superior to chemotherapy alone (p less than 0.05).