Previous studies have consistently found strong positive associations between smoking and Crohn's disease. The association between oral contraceptive use and Crohn's disease remains, however, controversial. In order to analyze whether smoking and oral contraceptive use are independent risk factors, a case-control study was performed. In 90 women with Crohn's disease and 90 community controls information was assessed about their smoking habits and their use of oral contraceptives. Smoking and oral contraceptive use were associated with one another. After adjusting for oral contraceptive use, the relative risk for smokers compared with nonsmokers was 3.0 (1.3-6.8). After controlling for smoking, the relative risk estimates for oral contraceptive use were for no use, 1-3 years, and >3 years of use 1. 0, 2.5 (1.0-6.6), and 4.3 (1.3-14.4), respectively. When oral contraceptive use was stratified by smoking habits, the data show that oral contraceptives only increased the risk for Crohn's disease in nonsmokers. From the lack of increase in risk for combined exposure, it is concluded that both factors might act through a common mechanism.