In a prospective cohort study, associations of resting heart rate with risk of coronary, cardiovascular disease, cancer, and all-cause mortality in age-specific cohorts of black and white men and women were examined over 22 years of follow-up. Participants were employees from 84 companies and organizations in the Chicago, Illinois, area who volunteered for a screening examination. Participants included 9,706 men aged 18-39 years, 7,760 men aged 40-59 years, 1,321 men aged 60-74 years, 6,928 women aged 18-39 years, 6,915 women aged 40-59 years, and 1,151 women aged 60-74 years at the baseline examination in 1967-1973. Vital status was ascertained through 1992. For fatal coronary disease, multivariate-adjusted relative risks associated with a 12 beats per minute higher heart rate (one standard deviation) were as follows: for men aged 18-39 years, relative risk (RR) = 1.27 (95% confidence interval (CI) 1.08-1.48); for men aged 40-59 years, RR = 1.13 (95% CI 1.05-1.21); for men aged 60-74 years, RR = 1.00 (95% CI 0.89-1.12); for women aged 40-59 years, RR = 1.21 (95% CI 1.07-1.36); and for women aged 60-74 years, RR = 1.16 (95% CI 0.99-1.37). Corresponding risks for all fatal cardiovascular diseases were similar to those for coronary death alone. Deaths from cancer were significantly associated with heart rate in men and women aged 40-59 years. All-cause mortality was associated with higher heart rate in men aged 18-39 years (RR = 1.11, 95% CI 1.01-1.20), men aged 40-59 years (RR = 1.16, 95% CI 1.11-1.21), and women aged 40-59 years (RR = 1.20, 95% CI 1.13-1.27). Heart rate was not associated with mortality in women aged 18-39 years. In summary, heart rate was a risk factor for mortality from coronary disease, all cardiovascular diseases, and all causes in younger men and in middle-aged men and women, and for cancer mortality in middle-aged men and women.