Fifty-six patients with extensive (52 with TNM stage III M1 disease and four with TNM stage III M0 disease) adenocarcinoma (46 patients) and large cell undifferentiated carcinoma (ten patients) of the lung were treated with combination chemotherapy consisting of 5-FU, vincristine, and mitomycin C (FOMi). The patients had not received prior chemotherapy. The overall response rate was 41% (23 of 56 patients). Four patients achieved a complete response and 19 achieved a partial response. In 12 patients the disease was stable. Response did not vary by cell type: adenocarcinoma, 18 of 43 patients (42%); large cell carcinoma, four of ten (40%); and alveolar cell carcinoma, one of three (33%). The response varied by initial performance status. For a Karnofsky score of greater than or equal to 70%, 20 of 41 patients (49%) responded, while for a Karnofsky score of less than 70%, three of 15 patients (20%) responded (P = 0.22). Survival was improved for responding patients regardless of initial performance status. The median survival duration was 24 weeks for the entire group of patients treated with FOMi. Survival of the responders (complete response plus partial response) was significantly improved over that of patients with progressive disease (28 weeks versus 13 weeks, respectively; P = 0.002). The FOMi combination was very well-tolerated. Nausea was common, but vomiting occurred in only four of 56 patients. Thrombocytopenia, requiring a reduction in the mitomycin C dose, developed after the third treatment course in 14 patients.