Thirty patients with advanced non-small cell lung cancer (NSCLC) were treated with cisplatin (P), mitomycin C (M), and 5-fluorouracil (5-FU) chemotherapy. Twelve patients (40%) achieved major responses to therapy (11 partial, one regression). The median duration of partial response was 20 weeks. Median survival for the entire group was 29 weeks. Toxicity with this combination was moderate, with myelosuppression being the most significant toxic effect. Acute hematologic toxicity was generally mild, with 74% of patients having a leukocyte nadir greater than or equal to 2000/microliter and 67% with a platelet count nadir of greater than or equal to 100,000/microliter. There were, however, two toxic deaths during periods of treatment-induced cytopenia, 40% of patients developed significant anemia necessitating blood transfusions, and 33% had episodes of prolonged neutropenia. Nonhematologic toxicities were generally mild, although one patient developed a cardiac arrest of unclear etiology during day 4 of cycle 3 of treatment and died, for a total treatment mortality rate of 10% (three of 30). This drug combination produced a response rate comparable to those noted with other two or three drug cisplatin-based regimens in NSCLC but does not appear to offer any substantial advantage given its moderate toxicity, short duration of response, and necessity for substantial hospitalization.