One hundred and eighteen patients with inoperable carcinoma of the lung were randomly selected for treatment with methotrexate, cyclophosphamide, procarbazine, and vincristine. These drugs were adminsitered simultaneously to one group of patients and sequentially to the second group. As the statistically sicame evident (51% vs. 21%), an additional 85 cases were treated in this manner without randomization. The objective clinical responses were associated with prolonged survival. A higher response rate with the simultaneous treatment was also evident in patients with anaplastic small cell carcinoma (65% vs. 36%) as well as those with epidermoid carcinoma (33% vs. 13%). These differences were not statistically significant. Toxicity remained within acceptable limits, with a 2% drug related mortality, and was similar in both treatment regimens. Initial performance status was definitely related to survival, but not to tumor response. Patients with epidermoid carcinomas showing stabilization of tumor growth under treatment had the longest survival. Maintenance therapy with continued four-drug polychemotherapy was not superior to single agent maintenance with cyclophosphamide.