In order to evaluate the determinants of cell type in patients with primary lung cancer, we compared smoking characteristics in 1,939 patients (1,474 men and 465 women). Patients with squamous cell carcinomas, adenocarcinomas, or small-cell carcinomas were eligible. This study did not consider smoking as a risk factor for lung cancer, as all subjects had a confirmed diagnosis. We were interested in smoking history and the pattern of smoking among those whose risk was 100 percent. Among these patients, we confirmed that a larger subset of nonsmoking individuals developed adenocarcinomas than squamous cell or small-cell carcinomas; however, the duration and intensity of cigarette smoking, as measured by pack-years, were not determinants of tumor cell type in male patients. Small-cell carcinomas in women were more strongly associated with cigarette smoking than either squamous cell carcinomas or adenocarcinomas. More than 3,500 different substances have been measured in tobacco smoke, including tumor initiators, promoters, and those involved in tumor progression. These data confirm the hypothesis that factors other than cigarette smoking are more likely to be involved in the initiation of adenocarcinomas than other cell types. Endogenous and exogenous factors related to gender may be more important than the duration or intensity of cigarette smoking.