Adrenal cancer is a heterogeneous group of neoplasms with unknown etiology. In search of risk factors, we conducted a case-control study based on data from the 1986 National Mortality Followback Survey, which included a questionnaire sent to the next of kin of almost 20,000 deceased adults (age > or = 25 year) in the United States. Information was obtained on a large number of items, including use of cigarettes, alcohol, oral contraceptives (OCs), height and weight and food consumption patterns. A total of 176 subjects who died of adrenal cancer (88 men and 88 women) and 352 controls (176 men and 176 women) who died of causes unrelated to smoking, drinking or OCs (for female controls) were included in the study. Although information on histologic type was not available, most cases were estimated from incidence surveys to be adrenocortical carcinoma, with a small percentage being malignant pheochromocytoma or neuroblastoma. An increased risk was associated with heavy smoking (> or = 25 cigarettes/day) among men (odds ratio [OR] = 2.0, 95% confidence interval [CI] 1.0-4.4) but not women. No clear association was seen for alcohol use, height and weight or food consumption patterns in either sex. Among women, increased risks were found for ever users of OCs (OR = 1.8, 95% CI 1.0-3.2) and especially those who used them before age 25 (OR = 2.5, 95% CI 1.2-5.5). When the analysis was restricted to subjects with spousal respondents, more pronounced risks were seen for ever users of OCs and for those who used OCs before age 25. Our findings suggest that cigarette smoking and use of OCs may increase the risk of adrenal cancer, but additional studies are needed with more detailed information on risk factors and histologic type of adrenal cancer.