Recent studies suggest that local levels of sympathetic nervous activity influence the growth of prostatic tissue. In several epidemiological studies, resting heart rate, an indicator of overall sympathetic activity, was positively associated with all noncardiovascular and cancer death among men. However, no previous analyses have focused on the specific relationship of heart rate to prostate cancer mortality. We studied 22,380 men enrolled in the Chicago Heart Association cohort from 1967-1973, who had heart rate (HR) determined by electrocardiogram. Mean length of follow-up (for mortality) was 19.2 years. We computed age-adjusted rates for prostate cancer death by variable of interest and fitted proportional hazards models to estimate relative risks (RRs) adjusted for potential confounders. In a model controlling for age, body mass index, blood pressure, serum cholesterol, smoking, postload plasma glucose, and years of education, the RR for a 10 beat/min higher HR was 1.26 (95% confidence interval = 1.04-1.51). Age-adjusted RRs across higher quintiles for HR were 1.00, 1.55, 1.85, 2.18, and 2.69 (P trend = 0.006). Survival curves indicated that the elevated risk was not confined to the early years of follow-up. Because little is known about factors that determine risk of prostate cancer death, these results could prove important even if due to an unmeasured etiological factor other than heart rate itself. The results are consistent with the hypothesis that local neurotrophic factors associated with sympathetic activity influence the progression of prostate cancer