Intake of calcium and/or dairy products has been associated with increased risk of prostate cancer in some epidemiological studies. One potential biological mechanism is that high calcium intake down-regulates 1,25 dihydroxy vitamin D(3), which may increase cell proliferation in the prostate. We examined the association between calcium, dairy intake, and prostate cancer incidence in the Cancer Prevention Study II Nutrition Cohort, a prospective cohort of elderly United States adults. Participants in the study completed a detailed questionnaire on diet, medical history, and lifestyle at enrollment in 1992-1993. After excluding men with a history of cancer or incomplete dietary information, 65,321 men remained for analysis. During follow-up through August 31, 1999, we documented 3811 cases of incident prostate cancer. Multivariate-adjusted rate ratios (RRs) were calculated using Cox proportional hazards models. Total calcium intake (from diet and supplements) was associated with modestly increased risk of prostate cancer [RR = 1.2, 95% confidence interval (CI) = 1.0-1.6 for >or=2000 versus <700 mg/day, P trend = 0.02). High dietary calcium intake (>or=2000 versus <700 mg/day) was also associated with increased risk of prostate cancer (RR = 1.6, 95% CI = 1.1-2.3, P trend = 0.10), although moderate levels of dietary calcium were not associated with increased risk. Dairy intake was not associated with prostate cancer risk. The association between prostate cancer and total calcium intake was strongest for men who reported not having prostate-specific antigen testing before 1992 (RR = 1.5, 95% CI = 1.1-2.0, P trend < 0.01 for >or= 2000 mg/day of total calcium; RR = 2.1, 95% CI = 1.3-3.4 >or=2000 mg/day of dietary calcium, P trend = 0.04). Our results support the hypothesis that very high calcium intake, above the recommended intake for men, may modestly increase risk of prostate cancer.