Forty-four previously untreated patients with advanced non-small-cell lung cancer were treated in a randomized trial comparing platinum (60 mg/m2), doxorubicin (40 mg/m2), and VP-16 (150 mg/m2) (PAV) with platinum (60 mg/m2), 4'-epidoxorubicin (50 mg/m2), and VP-16 (150 mg/m2) (PEV). The overall response rate was 10%. Major response rates were quite similar for the 21 patients treated with PAV (5%) and the 23 patients treated with PEV (18%) (p = 0.2). Of the 23 patients with assigned to PEV, two (9%) achieved complete responses for a median duration of 20 weeks and 44+ weeks. There was no significant difference (p = 0.75) in the median survival among patients treated with PAV (24 weeks) and those treated with PEV (20 weeks). Toxicity was generally mild and tolerable. The lack of response found in both arms of treatment caused the study to be terminated early. Some benefit could be appreciated in patients with limited disease and good Karnofsky performance status.