Fifty consecutive patients with extensive non-small cell carcinoma of the lung were randomized to one of two chemotherapeutic regimens. Twenty-three patients (group 1) received cyclophosphamide (600 mg/mg(2)), doxorubicin (40 mg/m(2)), and cisplatin (50 mg/m(2)) every 3 weeks; 27 patients (group 2) received cyclophosphamide (600 mg/m(2)), doxorubicin (40 mg/m(2)), and cisplatin (100 mg/m(2)) every 3 weeks. The objective response rates were 4% and 7% in groups 1 and 2, respectively. Median survival duration was 15.2 weeks (group 1) and 21.7 weeks (group 2; P greater than or equal to 0.3). Hematologic toxicity was minimal in group 1 and moderate in group 2. Renal toxicity was moderate in group 2 only. Combination chemotherapy with cyclophosphamide, doxorubicin, and cisplatin as used in this study is not superior to previous studies in this institution using cyclophosphamide as a single agent.