To determine whether prostaglandins (PG) contribute to captopril-induced natriuresis, 20 hypertensive subjects were assigned to one of the following three groups: group a, captopril (C) administration; group b, C + indomethacin (I); group c, I alone. Captopril was given in a dose of 100, 200, 400 mg/day and indomethacin in a dose of 100mg/day for one week. In group a (n = 10), natriuresis was clearly increased in the seven day periods with captopril in a dose of 200 and 400mg/day but not at 100mg/day. After captopril 200 or 400mg/day, but not 100mg/day, urinary PGE2 and PGI2 excretion significantly increased while filtration fraction fell due to a rise in renal plasma flow. Plasma aldosterone (PA) significantly decreased after C(p less than 0.05). In group b (n = 7), natriuresis disappeared during captopril 200 or 400mg/day and indomethacin administration even when PA decreased as in group a. In group c (n = 3), natriuresis was unchanged. In conclusion, natriuresis by C is critically dependent upon increased secretion of PG.