Small-cell lung cancer that progresses after initial response may still be sensitive to systemic treatment. This study assessed doxorubicin plus vinorelbine tartrate (Navelbine Injection) in patients who had no prior exposure to these agents. Treatment consisted of vinorelbine at 25 mg/m2 on days 1 and 8 and doxorubicin at 50 mg/m2 on day 1 of each 21-day cycle. The trial was stopped early because of excessive toxicity. The partial response rate was 26.7%. Toxicities included grade IV neutropenia in 73%, and febrile neutropenia and/or sepsis in 60%. Three patients died from sepsis during cycle 1. Performance status 2 was significantly associated with febrile neutropenia (p = 0.044). Although this regimen had some activity, the toxicity precluded further evaluation.