Possible development of proliferative lesions in bladders subjected to augmentation cystoplasty is a matter of concern for many clinicians. We have previously reported on the development of bladder papillomas in 5 of 15 rats approximately 18 months after gastrocystoplasty. We now report a followup study designed to investigate histopathological changes occurring in rat bladders approximately 2 years after augmentation cystoplasty using various gastrointestinal segments. Prepubescent Long-Evans female rats were randomly divided into 4 groups and underwent either gastrocystoplasty, ileocystoplasty, colocystoplasty or a sham operation (controls). Animals were sacrificed 14 to 27 months (average 21.5) postoperatively and bladders were examined histologically. Metaplastic and/or hyperplastic changes were observed in the gastrointestinal patches or surrounding urothelium in all bladders having undergone augmentation cystoplasty. Tumors occurred on or adjacent to the lumenal surface of the augmented segment in 4 of 10, 3 of 11 and 2 of 11 rats that underwent gastrocystoplasty, ileocystoplasty or colocystoplasty, respectively. None of the tumors was observed to invade blood vessels, lymphatics or the underlying muscle layers. However, histological features of malignancy characterized by varying degrees of cellular pleomorphism occurred in some tumors. Control rats (10) had only minor changes related to reapposition of tissues and remnants of suture. Possible etiologies and the potential significance of these augmentation cystoplasty related proliferative lesions are discussed.