Laboratory studies indicate that capsaicin, the hot-tasting component of chili peppers, may be carcinogenic. A population-based case-control study was conducted in Mexico City during 1989-1990 to evaluate the relation between chili pepper consumption and gastric cancer risk. The study included 220 incident cases and 752 controls randomly selected from the general population. Information was collected by interview. Chili pepper consumers were at high risk for gastric cancer compared with nonconsumers (age- and sex-adjusted odds ratio = 5.49, 95% confidence interval (CI) 2.72-11.06). Among consumers, there was a highly significant trend of increasing risk with increasing self-rated level of consumption (low, medium, and high) (p = 2 x 10(-7). The odds ratio for high-level consumers compared with nonconsumers was 17.11 (95% CI 7.78-37.59). However, when consumption was measured as frequency per day, a significant trend among consumers was not observed. Multivariable adjustment increased the magnitude of the chili pepper-gastric cancer association, but a significant trend among consumers (measured as frequency per day) was still not observed. Chili pepper consumption may be a strong risk factor for gastric cancer, but further studies are needed to test this hypothesis.