BACKGROUND: To examine the risk of prostate cancer and glucose tolerance in a large, racially diverse cohort. METHODS: We conducted a cohort study of 47,209 male members of Kaiser Permanente Northern California who had completed at least one Multiphasic Health Checkup (MHC) between 1964 and 1973. The MHC provided information on diabetes, serum glucose 1 h after a 75-g oral glucose challenge test, demographics, and other health conditions. Cox proportional hazards were used to estimate relative risks (RR) while adjusting for confounders. RESULTS: During a median follow-up of 18.4 years, a total of 2,833 men developed prostate cancer. At baseline, 4.6% (n = 2,159) of the cohort had diabetes and 33% had serum glucose of >or=200 mg/dL. After adjusting for age, race, birth year, and body mass index, RR (95% confidence interval) of prostate cancer associated with 1-h serum glucose >or=200 mg/dL and diabetes were 0.90 (0.81-1.01) and 0.71 (0.62-0.79), respectively, when compared with those with serum glucose <140 mg/dL. During the first 10 years of follow-up, risk was increased among those with serum glucose >or=200 mg/dL or diabetes [RR (95% confidence interval), 1.42 (0.95-2.13) and 1.56 (0.91-2.67), respectively]. In contrast, inverse associations between serum glucose >or=200 mg/dL and diabetes and prostate cancer risk were observed [0.87 (0.77-0.97) and 0.68 (0.52-0.88), respectively] when follow-up began 10 years after MHC. CONCLUSION: Our findings are consistent with the hypothesis that prostate cancer risk differs by time since diabetes diagnosis or occurrence of metabolic aberrations associated with impaired glucose tolerance.