Based on preclinical evidence of synergy, we performed a Phase I study of the combination of alpha-2 interferon and cisplatinum in patients with advanced malignancy. A fixed dose of 5 x 10(6) U/m2 alpha interferon was given three times weekly. Cisplatinum was given once weekly at dose levels of 5, 10, 20, 25, and 30 mg/m2. Dose-limiting toxicity consisted of flu-like symptoms and malaise leading to decreased performance status. Response was seen in a patient with metastatic melanoma. Recommended doses for Phase II study are 5 x 10(6) U/m2 of alpha-2 interferon three times weekly and 25 mg/m2 of cisplatinum once weekly.