Based on encouraging in vitro and in vivo data, 14 consecutive patients with measurable metastatic previously untreated colorectal carcinoma were treated with a combination of intravenous etoposide and subcutaneous alpha-interferon. Etoposide was given at 60 mg/m2 intravenously on days 1-5 and alpha-interferon at 5 million units/m2 subcutaneously on days 1-5; courses were repeated every 21 days. All 14 patients were evaluable for response and toxicity. None of the patients achieved a complete or partial remission. Toxicity of this combination was moderate. Our data suggest that this combination is ineffective against colorectal carcinoma.