Combining cisplatin and carboplatin may eliminate some of the toxic effects of each agent and permit the use of higher doses, because these agents have different pharmacodynamics and dose-limiting toxicities. We investigated the safety and efficacy of these agents in combination. The toxicity profile was evaluated in a Phase I trial in 18 patients with advanced non-small cell lung cancer (NSCLC). Carboplatin was administered in doses ranging from 200 to 400 mg/m2 on day 1 and cisplatin at a dose of 80 mg/m2 on day 3. Only one cycle of chemotherapy was administered. Thrombocytopenia was the dose-limiting toxic effect. The maximal tolerated dose of carboplatin was 350 mg/m2. We then investigated the efficacy of the optimal dose of this combined chemotherapy in a Phase II trial in 13 patients. We used a carboplatin dose of 300 mg/m2 for safety in the Phase II trial. Three of 13 patients developed grade 3-4 hematologic toxicity, which was improved without major complications. A partial response was observed in 5 of 13 patients (38.5%). Combination chemotherapy with carboplatin (day 1, 300 mg/m2) and cisplatin (day 3, 80 mg/m2) showed promising effects in patients with advanced NSCLC.