We administered chemotherapy consisting of a 21-day course of oral etoposide (50 mg/m2/day) and a 3-weekly dose of cisplatin (30-33 mg/m2/week) to 23 chemotherapy-naive patients with advanced non-small cell lung cancer (NSCLC). Six patients achieved a partial response (28.6%; 95% confidence interval, 11.3-52.2%), with a median response duration of 4 months and a median overall survival of 5 months. Besides alopecia, myelosuppression was the most significant drug-related toxicity. Observed side effects in 59 cycles of chemotherapy were granulocytopenia (<1,000/μl) in 23% of the treatment cycles, thrombocytopenia (<75,000/μl) in 25%, anemia (<10 g/dl) in 64%, and nausea-vomiting (grades ≥2) in 8%. Mild renal insufficiency (serum creatinine, 1.5-2.1 mg/dl) occurred in six patients. Three toxic deaths were observed during or immediately after cycle 1, and were related to granulocytopenia. We conclude that this regimen has modest activity in advanced NSCLC; but this therapeutic approach does not appear to produce a major improvement in the treatment of this disease. Thus, in advanced NSCLC, continued evaluation of new chemotherapeutic agents should remain the major emphasis of investigational therapy.