Aromatase inhibition by delta 1-testolactone (TL), 500 mg twice daily for 4 weeks, in nine patients with idiopathic oligospermia lowered circulating estradiol (E2) levels by about 30%, enhanced the secretion of follicle-stimulating hormone (+ 30%), 17-hydroxyprogesterone (17-OHP) (+ 40%), and testosterone (T) (+ 30%), but did not affect serum luteinizing hormone levels. Despite E2 lowering, there was an accumulation of 17-OHP over T, suggesting 17, 20-lyase inhibition. Unexpectedly, administration of TL almost completely deleted the T response to continuous luteinizing hormone-releasing hormone infusion present before TL therapy, despite similar gonadotropin release. Because the 17-OHP response to the luteinizing hormone-releasing hormone infusion was even higher during therapy, the 17,20-lyase lesion seemed aggravated despite substantial reduction of E2 levels. Although the present data suggest that estrogens play a less dominant role in the origin of the late steroidogenetic lesion than previously assumed, the suggestion also arises that TL per se, in addition to its antiestrogenic action, exerts an inhibiting effect on the 17,20-lyase locus, which may obscure the beneficial effect of reducing E2.