A case-control study was conducted to determine the significance of tobacco, alcohol and khat (Catha edulis) chewing habits in the development of oral leukoplakia among Kenyans aged 15 yr and over. In a house-to-house survey, 85 cases and 141 controls matched for sex, age and cluster origin was identified and compared for these risk factors. Smoking unprocessed tobacco (Kiraiku) with a relative risk (RR) of 10.0 (95% confidence interval (CI) = 2.9-38.4) and smoking cigarettes (RR = 8.4; 95% CI = 4.1-17.4) were the most significant factors. While the RR associated with smoking cigarettes alone was 4.5 (95% CI = 1.9-10.8), smoking of both products (RR = 15.2) suggested probable synergy or additive effects. Oral leukoplakia in 18 cases could not be attributed to smoking tobacco. Commercial beer, wines and spirits were relatively weak, but statistically significant, risk factors. Traditional beer, khat and chilies were not significantly associated with oral leukoplakia.