In an attempt to achieve adequate palliation in patients with small cell lung cancer (SCLC) while keeping toxicity to a minimum, we compared CVM (carboplatin/vinblastine/methotrexate) and standard therapy with ACE (doxorubicin/cyclophosphamide/etoposide). None of the 104 SCLC patients with limited or extensive disease who participated had received previous treatment. After stratification according to disease extent, patients were randomized to receive either CVM or ACE. The maximum number of chemotherapy courses was six. When response rates were compared, ACE was found to be somewhat superior to CVM in terms of objective response [CVM 67%, 95% confidence interval (CI) 54-79%; ACE 88%, 95% CI 80-97%; p = 0.06]; however, a significant difference was evident only among extensive-disease patients. Median response durations (CVM 6 months, 95% CI 5-8; ACE 5 months, 95% CI 3-6) and median survival times (CVM 8 months, 95% CI 7-10; ACE 7 months, 95% CI 4-9) were comparable. CVM met the goal of producing significantly less hematologic toxicity than occurred with ACE. Leukopenia affected 92% of ACE-treated patients and 48% of CVM-treated patients (p = 0.005), and was severe in 80% of the ACE group and 20% of the CVM group. Alopecia occurred much more frequently among those treated with ACE (91 vs. 24%; p < 0.001), as did infection (59 vs. 24%; p < 0.001). The selection of a specific chemotherapy regimen must be individualized. CVM may be appropriate for patients in whom intensive chemotherapy is contraindicated due to performance status, age, concomitant medical disease, or patient refusal.