Sildenafil citrate (Viagra) is widely used for the treatment of erectile dysfunction with various etiologies. The aim of the present study was the investigation of histopathotogical effects of sildenafil citrate on, rat corpus cavernosum using light and electron microscopical techniques. Twenty mate rats were divided into two groups. The first group (n = 10) was used as a Control and the second group (n = 10) was treated with sildenafil citrate. Penile tissue was collected, fixed with formalin and embedded in paraffin for light microscopy, or fixed with gluteraldehyde and osmium tetroxide and embedded in Epon for electron microscopy. Light microscopical analysis showed that the corpus cavernosum was elongated and the number of blood vessels was increased. The amount of connective tissue in the penis was increased and dense collagen and smooth muscle fibers were observed in treated rats. electron microscopical analysis showed that stromal. structures of the corpus cavernosum (collagen fibers and number of cellular elements) were increased in treated rats. Fibroblasts showed signs of activation and the number of other stromal cells was increased. Immature newly synthesized collagen fibers were observed and penetrated endothelial basement membranes. In addition, endothelial cells also showed signs of activation such as cytoplasmic granules in treated rats, whereas the surface area of blood vessels was increased and basement membranes were thickened. These histopathological changes due to treatment with sildenafil citrate indicate that prolonged use of sildenafil citrate may increase the risk of fibrosis in the penis. (C) 2003 Elsevier GmbH. All rights reserved.