The present study was designed to measure angiotensin-converting enzyme (ACE) activity in the human ovary and in serum and to relate this activity to age, serum estradiol levels, and uterine and endometrial pathology. ACE activity was determined in 56 females by a radiometric assay using [3H]hippuryl-glycyl-glycine as substrate. Ovarian ACE activity, but not serum ACE, was found to increase with age (P < 0.01) and was significantly greater in postmenopausal subjects (n = 31; 1.35 ± 0.05 nmol/mg · min) than in subjects with active ovaries (n = 21; 0.65 ± 0.2 nmol/mg · min; P = 0.0033). Ovarian ACE activities in fertile women in the preovulatory phase (n = 14) and the postovulatory phase (n = 7) were not statistically different (0.66 ± 0.23 and 0.60 ± 0.17 nmol/mg · min, respectively). Serum ACE activities were similar in females with active and nonactive ovaries (87.6 ± 5.0 vs. 81.7 ± 5.3 nmol/mL · min, respectively). Serum estradiol levels in fertile women were significantly higher than those in postmenopausal women (P = 0.0023). Serum estradiol levels were negatively correlated with age (r = - 0.46; P = 0.0041) and were not correlated with either serum ACE activity (r = 0.080; P = NS) or ovarian ACE activity. In summary, human ovarian ACE activity, but not serum ACE, is positively correlated with age. Serum estradiol levels decrease with age, but are not correlated with either ovarian or serum ACE activity. Endogenous serum estradiol levels had no apparent effect on ovarian or serum ACE activity. The presence of uterine pathology affects ovarian ACE activity. The cause of the increased ovarian ACE activity is not clear, but may be related to the aging process.