Because experimental and epidemiologic evidence indicates that the colon is particularly sensitive to stress, and because work conditions contribute to an individual's stress experience, we examined the relation of both job stress (defined in terms of perceived job demand and job control) and job social support to the risk of colon cancer in a large population-based case-control study (744 pairs) in Los Angeles. Controls were individually matched to cases on age, sex, and neighborhood. For jobs held 5 years before, participants in the lowest tertile of job control had a slightly increased risk when compared with those in the highest tertile (multivariate adjusted odds ratio = 1.3; 95% confidence interval = 1.0–1.6), but there was no evidence of a trend. Lower levels of job social support were associated with a decreased risk of colon cancer (odds ratio = 0.6 for lowest vs highest tertile; 95% confidence interval = 0.4–1.0). We saw no effect for job demand. The effect of job control appeared to be independent of the level of job demand. We found no consistent pattern of effects associated with jobs held 30 years before. These findings indicate that if job stress, as reflected by perceived job demand or control, is a determinant of colon cancer, it is probably not a strong one.