To test the hypothesis that environmental as well as genetic factors are important determinants of monovalent cation transport systems in humans, and to explore potential basic mechanisms of the alleged antihypertensive effects of habitual exercise, we studied the effects of a 12-week exercise program (45 minutes, 3-5 times per week) upon several membrane transport parameters in erythrocytes from a population of 63 adult men (30 normotensive subjects and 33 essential hypertensive patients). Subjects were randomly assigned into either an exercise group or a sedentary control group, and clinical and membrane transport parameters were measured at baseline and after 3 months. Exercising subjects demonstrated increases in maximal treadmill work capacity (p less than 0.001) and high-density lipoprotein cholesterol levels (p = 0.009) as well as decreases in heart rate at a fixed submaximal workload (p less than 0.05) and body weight (p less than 0.001) relative to the sedentary group. In conjunction with these well-described effects of exercise conditioning, the exercise group demonstrated a significant decrease in Na+-Li+ countertransport (p = 0.002), without significant changes in any other transport parameters measured. Blood pressure was not significantly altered in either group. We conclude that powerful environmental influences such as exercise training may act in concert with genetic factors to influence monovalent cation transport in humans and must be considered in further investigations of the pathophysiological linkage between altered monovalent cation transport and essential hypertension.