The effect of oral contraception and of exercise on the renin-angiotensin system was studied in 20 highly trained athletes, of whom 10 were ingesting oral contraceptives (users) and 10 were not (nonusers), and in 24 sedentary age-matched healthy female subjects, of whom 13 were users and 11 were nonusers. No training-related effects were observed with the exception of renin substrate, which was significantly higher in the athletes. The plasma concentrations of active renin and of trypsin-activatable prorenin were significantly lower in the subjects taking oral contraceptives. Renin substrate, however, was significantly higher in the oral contraceptives group. No difference in plasma renin activity (PRA) was observed between users and nonusers. The results demonstrate the well-known estrogen-induced stimulation of renin substrate synthesis by the liver and suggest a decreased secretion of renin by the kidney. Exhaustive exercise of short duration, performed by the trained athletes only, stimulated the renin-angiotensin system. An increase in PRA and in active renin concentration was observed. The prorenin concentration did not change significantly. The magnitude of the exercise-induced changes was considerably influenced by oral contraceptive medication. Nonusers showed a significantly greater increase in PRA and active renin and total renin concentration than users. Renin substrate decreased significantly during exercise in the nonusers only. These results demonstrate that oral contraceptives have a suppressive effect on renin secretion at rest, an effect that becomes more prominent during exercise, i.e., physiological stimulation.