Among 360 patients with small cell lung cancer treated in National Cancer Institute therapeutic trials from 1973 to 1982, 40 were two-year cancer-free survivors. Of these 40 patients, six had later development of non-small-cell lung cancer at 3.5 to 8.0 years (median 5.1) after the diagnosis of small cell lung cancer. Three had the second malignant tumor in the contralateral lung, one in a different lobe, and two in the same lobe as the initial small cell lung cancer. Ten patients had relapses of small cell lung cancer at 2.1 to 6.2 years (median 3.2) from diagnosis. Three recurrences were in the same site or lobe as the initial lesion, four in the same lobe and in sites outside the thorax, and three solely in sites outside the thorax. It is concluded that these non-small-cell lung cancers usually represent second primary lung tumors and that most late small cell lung cancers represent relapses occurring up to 6.2 years from diagnosis. In this study, the risk of development of non-small-cell lung cancer after two years of disease-free survival following small cell lung cancer is 4.4 percent per person-year, approximately 10 times higher than the rate of 0.5 percent previously determined in screening studies of men at high risk for lung cancer. Non-small-cell lung cancer represents more than a third of lung cancer deaths in patients with small cell lung cancer surviving beyond two years from diagnosis and more than half of lung cancer deaths beyond three years. It is recommended that all patients treated for small cell lung cancer discontinue smoking.