We recently established diagnostic criteria for granular cell changes in the distal female reproductive tract of rats. In a review of control animals from 9 carcinogenicity studies, we found that approximately 23% of animals had granular cell alterations. Because estrogen may play a role in the pathogenesis of granular cell alterations, we reviewed tissue sections from carcinogenicity studies with 2 aromatase inhibitors and found compound-related decreases in the incidence of granular cell changes. Since these aromatase inhibitors selectively prevent the conversion of androgenic steroids to the corresponding estrogens, these data further suggest that estrogen may play a role in the pathogenesis of granular cell tumors of the reproductive tract of rats.