PURPOSE: The purpose of this study was to examine the long term relationships between total physical activity and mortality from all causes and coronary heart disease (CHD) in the general population. METHODS: A prospective design was used, following participants for 29 years, beginning, in 1960. The study population consisted of a randomly selected sample of white male (n = 698) and female (n = 763) residents of Buffalo, New York with a 79.0% participation rate and follow-up rates of 96.0% and 90.2% in males and females, respectively. At baseline, comprehensive information was obtained regarding participants' usual physical activity at work and during leisure time. RESULTS: As of December 31, 1989, three hundred and two (43.3%) men and 276 (41.0%) women died, 109 (15.6%) and 81 (10.6%) from CI-ID, respectively. In men, a significant interaction was found between activity and body mass index (BMI) for both outcomes, In women, a significant activity by age interaction was observed. In non-obese men (BMI < 27.02), activity was inversely associated with all cause [relative risk (RR) = 0.59; 95% confidence interval (CI), 0.39-0.89] and CHD mortality (RR = 0.39; 95 % CI, 0.18-0.83), independent from the effects of age and education. No such associations were found in obese men and increased risks could not be ruled out. Among women, younger participants (age < 60 years) had a significantly reduced risk of CHD death with increased activity (RR = 0.26; 95% CI, 0.07-0.99). No other significant associations were observed. CONCLUSIONS: Physical activity favorably influences mortality risks in non-obese men and younger women. Gender-specific factors should be considered for potential effect modification. (C) 1999 Elsevier Science Inc. All rights reserved.