Thirty-eight patients with advanced measurable non-small cell carcinoma of the lung (20 adenocarcinoma, 13 epidermoid carcinoma, 5 large cell anaplastic carcinoma) were treated with alpha(leukocyte)-interferon. Patients received 3 X 10(6) units intramuscularly 5 days out of 7. Patients were treated for 12 weeks or as modified for disease progression or positive response to therapy. In 37 patients evaluable for response, one partial response was observed (adenocarcinoma). Toxicity included fever and malaise, leukopenia, thrombocytopenia, nausea-vomiting, and hepatic toxicity. One additional patient with previous cardiac and pulmonary disease had a cardiorespiratory arrest several hours after his first interferon injection. The relationship between those events is not clear. As administered, alpha-interferon showed no meaningful activity as therapy for non-small cell carcinoma of the lung.