The effect of an angiotensin-converting enzyme inhibitor, lisinopril, on gonadal hormones was assessed in 20 patients with essential hypertension. A daily dose of 5 to 20 mg of lisinopril was administered for 6 mo. In male patients, the free testosterone (f-T) concentration decreased significantly (before, 13.8+/-2.4 pg/ml; after, 9.9+/-1.5 pg/ml: mean +/- SEM, p < 0.05), whereas the plasma total testosterone (T), estradiol (E2), and sex hormone binding globulin (SHBG) concentrations were not significantly affected. Lisinopril had no effect on plasma T, f-T, or E2 concentrations in female patients, but significantly increased the plasma SHBG concentration (before, 48.0 6.1 nmol/l; after, 62.7+/-6.7 nmol/l: p < 0.01). The results of this preliminary study suggest that lisinopril affects plasma f-T and SHBG concentrations. The clinical implications of lisinopril-induced changes in plasma f-T and SHBG concentrations remain to be clarified.