To examine dietary fat and meat intake in relation to risk of type 2 diabetes. We prospectively followed 42,504 male participants of the Health Professionals Follow-Up Study who were aged 40-75 years and free of diagnosed diabetes, cardiovascular disease, and cancer in 1986. Diet was assessed by a validated food frequency questionnaire and updated in 1990 and 1994. During 12 years of follow-up, we ascertained 1,321 incident cases of type 2 diabetes. Intakes of total fat (multivariate RR for extreme quintiles 1.27, CI 1.04-1.55, P for trend=0.02) and saturated fat (1.34, 1.09-1.66, P for trend=0.01) were associated with a higher risk of type 2 diabetes. However, these associations disappeared after additional adjustment for BMI (total fat RR 0.97, CI 0.79-1.18; saturated fat 0.97, 0.79-1.20). Intakes of oleic acid, trans-fat, long-chain n-3 fat, and alpha-linolenic acid were not associated with diabetes risk after multivariate adjustment. Linoleic acid was associated with a lower risk of type 2 diabetes in men <65 years of age (RR 0.74, CI 0.60-0.92, P for trend=0.01) and in men with a BMI <25 kg/m(2) (0.53, 0.33-0.85, P for trend=0.006) but not in older and obese men. Frequent consumption of processed meat was associated with a higher risk for type 2 diabetes (RR 1.46, CI 1.14-1.86 for > or = 5/week vs. <1/month, P for trend <0.0001). Total and saturated fat intake were associated with a higher risk of type 2 diabetes, but these associations were not independent of BMI. Frequent consumption of processed meats may increase risk of type 2 diabetes.