The relation between physical fitness and cardiovascular disease mortality was examined in US railroad workers, as a part of the Seven Countries Study. A cohort of 3,043 white, middle-aged men initially aged 22-79 years were first examined in 1957-1960 and re-examined in 1962-1964. Men with clinically diagnosed cardiovascular disease (n = 465) were excluded from this study. This cohort was followed until death or 1977. Mortality was monitored through the Railroad Retirement Board. Physical fitness was ascertained by a sub-maximal treadmill test administered in a Pullman Car converted to a survey laboratory. Exercise heart rate was directly and significantly related to coronary heart disease mortality, cardiovascular disease mortality, and all-cause mortality after adjusting for age. These relations were greatly attenuated when adjusted for blood pressure level. The risk for coronary heart disease when an exercise test heart rate of 135 beats per minute was compared with a rate of 105 beats per minute was 1.43, after adjusting for age, and 1.20, after adjusting for blood pressure, serum cholesterol levels, and smoking, as well as age. Results from this study suggest that middle-aged men with lower levels of physical fitness, as shown by higher sub-maximal exercise test heart rates, are at greater risk of dying of coronary heart disease, cardiovascular disease, and all causes in an average follow-up of 20 years. This greater risk is largely due to higher blood pressure levels.