The subacute administration of estradiol-17 beta was shown to be a potent inducer of an inflammatory response specific to the lateral prostate of the castrated Wistar rat. The subsequent administration of dihydrotestosterone restored the wet weight of the gland while maintaining the inflammation established with estrogen treatment. These changes are histologically similar to a spontaneously arising nonbacterial prostatitis previously reported by others in the aging rat lateral prostate. When the same hormones were administered on a chronic basis, the intensity of the inflammation increased with time and was accompanied by a fibromuscular proliferation that consisted of fibroblasts, smooth muscle cells, and collagen. These chronic changes correlated well with studies by other investigators on human benign prostatic hyperplasia (BPH) where certain forms of BPH were associated with a significant degree of inflammation and fibromuscular growth. The present studies therefore establish a model system for the hormonal induction of an inflammatory reaction in the rat lateral prostate that precedes and could be causally related to proliferative responses in the fibromuscular stroma. The potentially important similarities that exist between these experimental findings and the human problems of nonbacterial prostatitis and benign prostatic hyperplasia warrant additional study.