To assess the immediate and long-term effects of exercise on factors regulating blood flow, we measured plasma viscosity (eta p) and plasma renin activity (PRA) in 17 trained runners and 16 sedentary healthy subjects before and 10 min after graded treadmill exercise. Resting eta p was lower in runners primarily because of significantly lower fibrinogen concentration. Compared to nonrunners with similar 24-h urine electrolyte excretion rates, runners were characterized by lower PRA at rest. In view of the overall correlation between heart rate and PRA before exercise, reduced adrenergic tone was probably a major factor contributing to the lower PRA in runners. After exercise, plasma viscosity and PRA exceeded control levels, and were similar in magnitude in runners and sedentary subjects. Changes in plasma viscosity were less than expected from the degree of hemoconcentration, primarily because enhanced fibrinolysis maintained fibrinogen level constant. To the extent that plasma viscosity affects viscous flow resistance, the results suggest that tissue perfusion and oxygen delivery rate at rest are greater in trained runners than in sedentary subjects, but these variables become similar after maximum exertion.