The combinations of doxorubicin (40 mg/m2 iv every 3 weeks) and mitomycin (12 mg/m2 iv every 6 weeks) or cisplatin (80 mg/m2 iv every 3 weeks X 3, then every 6 weeks) and etoposide (80 mg/m2 iv on Days 1-3 every 3 weeks X 3, then every 6 weeks) were evaluated in a randomized phase II trial in 77 patients with measurable or evaluable non-small cell lung cancer. No patient had been pretreated with prior chemotherapy. The overall response rate for the doxorubicin and mitomycin regimen was 11% and for the cisplatin and etoposide regimen was 23%. Responses lasted a median of 5.5 months. Median survival was 7.0 months for the doxorubicin and mitomycin regimen and 8.0 months for the cisplatin and etoposide regimen. One treatment-related death was observed after doxorubicin and mitomycin in a patient who had received radiation therapy immediately prior to study entry. Otherwise, the hematologic toxicity of both chemotherapy regimens was moderate, with only six patients (10%) having World Health Organization grade 3 toxicity and no patients having World Health Organization grade 4 toxicity. However, subjective tolerance gastrointestinal upset) of the cisplatin and etoposide combination was poor.