Treatment of male rats and dogs with CGP 32,349 (formestane), a steroidal aromatase inhibitor, and CGS 20,267 (letrozole), a non-steroidal aromatase inhibitor, induced different alterations in testicular interstitial Leydig cells in the two species. Whereas in dogs Leydig cells were hypertrophic and hyperplastic, in rats either no effect (CGS 20,267) or atrophy of Leydig cells (CGP 32,349) was reported. The different response of the two species can be explained by different regulating mechanisms of gonadotropin secretion by the anterior pituitary.