Eighteen patients with multiple recurrences of malignant melanoma without evident distant spread were randomly assigned to treatment with either intralesional Bacillus Calmette-Guerin (BCG) or intralesional dinitrochlorobenzene (DNCB). Both agents were able to destroy approximately 90% of the injected intradermal nodules. Intradermal disease was more easily obliterated than subcutaneous disease with intralesional treatment with either agent, and local control of satellitosis with elimination of all clinically evident tumor was achieved in the patients who had intradermal without subcutaneous satellitosis, regardless of whether the patient was receiving BCG or DNCB. The clinical courses of the treated patients were essentially the same. Although PHA reactivity was depressed, the patients in both groups were responsive to recall and melanoma skin test antigens, demonstrated leukocyte migration inhibition with melanoma antigen and were generally within normal limits when assayed for 29 degrees C E rosettes. Our study demonstrated a dramatic difference in toxicity between the two intralesional agents without a similar difference in therapeutic efficacy or immune testing.