Peyronie's disease is an idiopathic, localized connective tissue disorder of the penis, involving the tunica albuginea of the corpus cavernosum and adjacent areolar space. Current proposals as to the origin of Peyronie's disease suggest that fibrosis and collagen changes of the tunica are the result of an inflammatory process following vascular trauma. Our laboratory and other investigators have recently proposed an animal model for the study of Peyronie's disease. When transforming growth factor-beta1 (TGF-beta1) was injected into the rat tunica albuginea, tissue fibrosis was observed at 6 weeks. Therefore, our aim was to assess arginase II, endothelial and inducible nitric oxide synthase isoforms, and nitrotyrosine levels--all factors involved in inflammatory reactions--in the cavernosal tissue of saline-injected and TGF-beta1-injected rats after 6 weeks in order to evaluate the roles these enzymes may play in the induction of a Peyronie's-like condition in the rat. To examine the expression of endothelial nitric oxide synthase (eNOS), iNOS, and arginase II protein, and mRNA in the corpus cavernosum, immunoblot analysis, and reverse transcriptase-polymerase chain reaction were performed. We also determined immunohistochemically the expression of nitrotyrosine, a marker of peroxynitrite formation, in the rat penis. After 6 weeks, iNOS protein and gene expression was up-regulated and eNOS protein and gene expression was down-regulated in the corpora cavernosa of the TGF-beta1-injected penises. Furthermore, arginase II protein expression as well as immunohistochemical localization of nitrotyrosine was significantly higher in the TGF-beta1-injected corpora cavernosa. These results suggest that iNOS is the key control element for peroxynitrite formation, arginase II expression, and eNOS down-regulation in the induction of a Peyronie's-like condition in the rat.