The efficacy and toxicity of chronic administration of oral etoposide was evaluated in 61 patients with inoperable non-small-cell lung cancer (NSCLC). Ten patients received previous chemotherapy, 15 received radiotherapy, and one received both treatments. Twenty-four patients had concurrent cardiac and/or pulmonary impairment, which precluded more intensive treatment. Etoposide was given orally, 100 mg daily for 7 consecutive days and consequently 100 mg every other day for 14 more days in a 28-day schedule. Partial response was observed in 17 patients (28%; 95% confidence interval, 17-39%) and stable disease in 21 (34%). The median duration of response was 6 months (range, 2-34 months). The median survival for responders was 22 months and that of nonresponders was 7 months (p < 0.001). The median survival for all patients was 9 months (range, 1-35 months; 95% confidence interval, 5.69-12.31%). Toxicity was acceptable. Other than alopecia, which was observed in all patients, myelotoxicity was the most common toxicity--particularly leukopenia, which was severe in nine patients. Other less common toxicities included nausea and vomiting, stomatitis, anorexia, and neurotoxicity and were mild. No treatment-related deaths were observed. In conclusion, the regimen was effective and well tolerated with significant survival benefit for the responders. It represents an interesting therapeutic approach, especially in the elderly.