Based on studies that show gender differences in cigarette smoking and lung cancer risk, we hypothesized that sex differences also exist in the risk for cancer of the oral cavity and pharynx. A hospital-based study of 1009 patients with oral neoplasia and 923 age-matched controls was conducted from 1981-1990. All subjects were interviewed directly with an extensive questionnaire containing items on tobacco smoking, alcohol consumption, and occupational exposures. Using a cumulative lifetime measure of exposure to cigarette tar, the adjusted odds ratio for men, according to increasing quartile of tar consumption and relative to never smokers, was 1.0 [95% confidence interval (CI), 0.6-1.6) for the lowest category, 0.9 (95% CI, 0.6-1.6) for the second category, 1.6 (95% CI, 1.0-2.5) for the third category, and 2.1 (95p5 CI, 1.4-3.2) for the highest category. Among women, the corresponding odds ratios were 1.8 (95% CI, 1.1-3.0), 2.8 (95% CI, 1.6-4.9), 3.2 (95% CI, 1.9-5.6), and 4.6 (95% CI, 2.5-8.7). The linear increase in risk was significantly higher for women than for men. Among nonsmoking cases, there was a significantly higher proportion of women than men over the age of 50 years. This was consistent for all subsites within the oral cavity. These findings support the hypothesis that there are gender differences in the smoking-related risks for oral cancer and in the risk for nonsmoking-related oral cancer as well. The role of nutrition in relation to these findings is discussed.