This study examines the effect of sodium homeostasis on the plasma aldosterone, renin, and PRL responses to the dopamine antagonist metoclopramide in normal individuals. Responses to metoclopramide were evaluated after receiving a 10-meq sodium, 80-meq potassium diet for 5 days and after receiving a 200-meq sodium, 80-meq diet for 5 days. On both occasions, the subjects had reached sodium equilibrium states, as determined by urinary sodium measurements, at the time that they received metoclopramide. Maximum absolute incremental aldosterone responses to metoclopramide were considerably greater (P less than 0.001) in the subjects after 5 days on a 10-meq sodium intake (23.2 +/- 2.0 ng/dl) than after 5 days on a 200-meq sodium intake (6.6 +/-0.9 ng/dl). Greater PRL and PRA responses (P less than 0.05) were also noted with low (10 meq) daily sodium intake, although the influence of sodium intake was less than that observed on the aldosterone response to metoclopramide. PRA responses to metoclopramide occur late (45 min) compared to aldosterone and PRL responses, which were noted 5 min after drug administration, suggesting an indirect effect of dopamine in modulating renin secretion. The proportion of total renin which was inactive was greater with the higher sodium intake. These data suggest that sodium homeostasis may influence dopaminergic modulation of renin, aldosterone, and PRL secretion and may effect the interrelationship between active and inactive renin.