The possible interactions between the prostaglandin and dopamine systems in the control of prolactin, renin and aldosterone secretion were studied in seven normal subjects. The responses to the dopamine antagonist, metoclopramide (10 mg. i.v.) were studied before and after prostaglandin inhibition with indomethacin (50 mg every 8 hr for 3 doses) while the subjects were in balance on a low sodium (less than 10 meq/day) diet. Urinary prostaglandin E excretion was reduced 61% (p less than 0.05) with indomethacin administration. Plasma renin activity (active and inactive) was not significantly affected by indomethacin treatment. However, the renin activity following metoclopramide tended to rise before, and fall after, indomethacin. Plasma aldosterone increased rapidly after metoclopramide, peaking at ten to fifteen minutes (p less than 0.01). There was no significant difference between the control and indomethacin days. Prolactin increased following metoclopramide, peaking at fifteen to thirty minutes (p less than 0.01). The prolactin response was significantly (p less than 0.05) decreased by indomethacin at four of six time points and the area beneath the response curve was significantly (p less than 0.05) blunted (3048 +/- 132 versus 3882 +/- 146 ng. min/ml). The results suggest that a cyclooxygenase product may modulate the prolactin response to dopamine antagonism. Although the renin response to metoclopramide was altered by indomethacin, the aldosterone response to dopamine antagonism is not medicated by cyclooxygenase products or the renin-angiotension system.