The authors examined the associations between fruit and vegetable intakes and risk of colorectal cancer in the NIH-AARP Diet and Health Study. Diet was assessed with a food frequency questionnaire at baseline. Relative risks and 95% confidence intervals were estimated by using the Cox proportional hazards model. During 5-year follow-up of 488,043 men and women aged 50-71 years, 2,972 incident colorectal cancer cases were identified. The respective 10th and 90th percentiles of total fruit and vegetable intake (servings/1,000 kcal per day) were 1.4 and 5.2 for men and 1.8 and 6.5 for women. Compared with that for the lowest quintile of vegetable intake, the multivariate relative risk for the highest quintile was 0.82 (95% confidence interval: 0.71, 0.94) for men and 1.12 (95% confidence interval: 0.90, 1.38) for women. Increased risk of colorectal cancer was observed for very low intake of total fruits and vegetables by men (multivariate relative risk for <1 vs. > or =2.0 servings/1,000 kcal per day = 1.26, 95% confidence interval: 1.03, 1.54). Among subgroups of vegetables, green leafy vegetables were associated with a lower risk of colorectal cancer for men (multivariate relative risk for the highest quintile vs. the lowest = 0.86, 95% confidence interval: 0.74, 0.99). Intake of fruits was not related to risk of colorectal cancer in men or women.