Partially purified human leukocyte (alpha) interferon was administered i.m. at a dose of 3 x 10(6) units/day to 19 patients with metastatic renal cell carcinoma. Five patients (26%) showed partial responses; two patients (10.5%), objective minor responses; three patients (16%), mixed effects (evidence of biological effect with regression of some lesions but concomitant progression); two patients (10.5%), disease stabilization; and seven patients (37%), progressive disease. All tumor responses were seen in lung or mediastinal metastases. Tumor response significantly correlated with interferon-induced leukopenia and granulocytopenia and with pretreatment performance status. Antibodies to interferon were found in one patient prior to treatment. We concluded that interferon is a potential active antitumor agent in patients with renal cell carcinoma.