Fifty patients with small-cell lung cancer (SCLC) were treated with teniposide (VM26) at 120 to 140 mg/m2 on days 1, 3, and 5, every 3 weeks. Twelve elderly patients were administered VM26 as first-line chemotherapy. Toxicity was manageable, myelosuppression being the major side effect. The response rate for 44 evaluable patients was 34% (36% for untreated patients); the median durations of response and survival were 230 and 208 days, respectively. Effectiveness of prior chemotherapy and time from last administration was found to influence patient response to VM26: 42% of responders to prior chemotherapy responded to VM26, while 0% of the nonresponders to prior chemotherapy responded to the new agent. Moreover, among patients pretreated with chemotherapy, 12% of those recently treated (earlier chemotherapy ending less than or equal to 2.6 months before administration of VM26) responded to VM26, while 53% of patients treated greater than 2.6 months earlier responded to VM26. Survival was influenced by common prognostic factors (performance status, weight loss, prior chemotherapy exposure). Selection of pretreated patients by type of exposure to prior chemotherapy may help in the testing of new drugs in this disease.