OBJECTIVE - Intake of carbohydrates that provide a large glycemic response has been hypothesized to increase the risk of NIDDM, whereas dietary fiber is suspected to reduce incidence. These hypotheses have not been evaluated prospectively. RESEARCH DESIGN AND METHODS - We examined the relationship between diet and risk of NIDDM in a cohort of 42,759 men without NIDDM or cardiovascular disease, who were 40-75 years of age in 1986. Diet was assessed at baseline by a validated semiquantitative food frequency questionnaire. During 6-years of follow-up, 523 incident cases of NIDDM were documented. RESULTS - The dietary glycemic index (an indicator of carbohydrate's ability to raise blood glucose levels) was positively associated with risk of NIDDM after adjustment for age, BMI, smoking, physical activity, family history of diabetes, alcohol consumption, cereal fiber, and total energy intake. Comparing the highest and lowest quintiles, the relative risk (RR) of NIDDM was 1.37 (95% CI, 1.02-1.83, P trend = 0.03). Cereal fiber was inversely associated with risk of NIDDM (RR = 0.70; 95% CI, 0.51-0.96, P trend = 0.007; for >8.1 g/day vs. < 32 g/day) The combination of a high glycemic load and a low cereal fiber intake further increased the risk of NIDDM (RR = 2.17, 95% CI, 1.04-4.54) when compared with a low glycemic load and high cereal fiber intake. CONCLUSIONS - These findings support the hypothesis that diets with a high glycemic load and a low cereal fiber content increase risk of NIDDM in men. Further, they suggest that grains should be consumed in a minimally refined form to reduce the incidence of NIDDM.