This phase II trial investigated the activity and toxicity of CODE (cisplatin, vincristine, doxorubicin, etoposide) chemotherapy with the addition of granulocyte colony-stimulating factor (G-CSF) in patients who had chemotherapy-naive, advanced, or metastatic non-small-cell lung cancer. Treatment consisted of cisplatin, 25 mg/m2, administered weeks 1 through 9; vincristine, 1 mg/m2, weeks 1, 2, 4, 6, and 8; doxorubicin, 40 mg/m2, weeks 1, 3, 5, 7, and 9; and etoposide, 80 mg/m2 intravenously day 1 and 160 mg/m2 orally, days 2 and 3 on weeks 1, 3, 5, 7, and 9. Granulocyte colony-stimulating factor, 5 microg/kg, was administered subcutaneously on all days that patients were not receiving chemotherapy. From April 1992 through April 1993, 42 patients were entered on study. The principal toxicities were hematologic. Grade 3-4 anemia was seen in 21 patients. Grade 3-4 thrombocytopenia was seen in 9 patients. Grade 3-4 neutropenia occurred in 29 patients. Eight patients experienced a neutropenic febrile episode requiring antibiotics. Nonhematologic toxicities included weight loss and fatigue. Responses were seen in 10 of 42 patients, for an overall response rate of 24% (95% confidence interval, 12%-39%) and a median survival of 7.1 months. The CODE chemotherapy regimen has activity similar to other previously described cisplatin-based regimens, with a significant amount of both hematologic and nonhematologic toxicity. Its continued use in patients who have previously untreated non-small-cell lung cancer cannot be recommended, based on the results of this study.