Abnormal mammary enlargement, characterized microscopically by hyperplasia of both epithelial and mesenchymal tissues, was studied in 26 cats which were mostly young, sexually intact females. Clinicopathologic data indicated that mammary hypertrophy was likely progesterone-dependent. Administration of progestins preceded this condition in 5 cats, 4 of which were neutered. Serum progesterone concentrations (6.7 ng/ml) were increased in 1 of the 3 cats tested. Estrogen receptors were not found in the cytosols or nuclei of mammary tissues in the 2 cats studied. However, there were convincing 4S [3H]progesterone or 5S [3H]R5020 binding peaks which were suppressible by nonlabeled progestins. Progesterone receptors were measured at 14.9 and 8.6 fm/mg of protein, respectively. The apparent influence of progesterone, whether present as exogenous therapy in the male or female or as endogenous steroid of ovarian origin, has thus been demonstrated directly and indirectly in cats with mammary hypertrophy.