The combination treatment of mitomycin C (M), vincristine (V), and cisplatin (P) (MVP) in 63 patients with advanced non-small cell lung cancer (NSCLC) were evaluated for their potential synergistic cytotoxicity. The overall response rate was 43% (27/63); in the 54 eligible and evaluable patients, the response rate was 50% (27/54). Responses were observed in all cell types and disease sites. Cell type; performance status of 0, 1, or 2; sex; and age younger or older than 60 years did not significantly influence the response rate. However, patients with prior radiation had significantly more treatment failure than those without. The dose-limiting side effects in these 54 patients were myelosuppression (40%), pulmonary fibrosis (9%), peripheral neuropathy (6%), and intractable nausea and vomiting (4%). The degree of leukopenia (P less than 0.01) but not of thrombocytopenia increased significantly in patients who had received prior radiotherapy. One patient died of marked thrombocytopenia and one of fulminant hepatitis. Patients who responded lived significantly longer than those who did not (P less than 0.004). A majority of the responders (82%) also achieved symptomatic palliation. With appropriate dose modification and supportive care, MVP was tolerable. Further trials with this regimen or a modified version are worth consideration.