Several epidemiological studies have identified an association between nonsteroidal anti-inflammatory drug (NSAID) use and colorectal cancer risk in women. We examined this association in a population-based case-control study in Wisconsin women. Between 1991 and 1992, 184 women ages 40-74 years with colorectal cancer were identified through the statewide cancer registry and 293 population-based control women were randomly selected via telephone. Regular NSAID use was defined as at least twice weekly for 12 months or longer. After adjusting the data for age, controls were more likely than cases to report regular NSAID use (38 versus 27%). Following adjustment for age, prior sigmoidoscopy use, family history of large bowel cancer, and body mass index, women who regularly used NSAIDs were approximately one-third less likely to be diagnosed with colorectal cancer compared to women who did not use NSAIDs [odds ratio (OR), 0.65; 95% confidence interval (CI), 0.40-1.03]. A statistically significant effect of duration of use was identified, although the ORs did not show a consistent trend. No significant effect of frequency of NSAID use was observed. When the type of NSAID used was examined (aspirin or nonaspirin), subjects who used nonaspirin compounds had a statistically significantly lower risk of colorectal cancer (OR, 0.43; 95% CI, 0.20-0.89), compared to nonusers, whereas aspirin users had only a small, nonsignificant reduction in cancer risk (OR, 0.79; 95% CI, 0.46-1.36). These data add support to the hypothesis that regular NSAID use is associated with lower colorectal cancer risk in women and suggest that the type of NSAID used may be important.