Sixty-five patients (20 patients who had had prior radiotherapy and 45 patients who had not had prior radiotherapy) were entered into a study evaluating escalating doses of etoposide and mitomycin in the treatment of non-small-cell lung cancer (NSCLC). Twenty-two percent of patients who had not received prior radiotherapy responded to the chemotherapy, compared with 5% of patients who had received prior radiotherapy. The best response rate and median survival time was 30% and 31.9 weeks, respectively, seen in three of 10 patients receiving mitomycin 10 mg/M2 i.v. day 1 and etoposide 100 mg/M2 i.v. days 1-3. The major toxicity was hematologic--mainly leukopenia, in 59% of patients who had had no prior radiation therapy and were receiving mitomycin 10 mg/M2 i.v. day 1 and etoposide 150 mg/M2 i.v. days 1-3 (grade 3 and 4 hematologic toxicity). The mitomycin-etoposide drug combination has some activity in patients with NSCLC who have not received prior radiotherapy. The recommended starting dose is mitomycin 10 mg/M2 i.v. day 1 and etoposide 100 mg/M2 i.v. days 1-3, administered every 4 weeks.