Cyclophosphamide is an alkylating agent used intravenously or orally in the treatment of both malignant and nonneoplastic diseases. A known adverse effect of such treatment is hemorrhagic cystitis. A series of 100 patients with hemorrhagic cystitis induced by cyclophosphamide was studied. Major symptoms were gross hematuria (78%) and irritative voiding symptoms (45%). Microhematuria developed in 93% of patients. Hemorrhagic cystitis developed at significantly lower doses and shorter durations of therapy in patients treated intravenously than in patients treated orally. Cystectomy was required in nine patients and bladder cancer developed in five. Urine cytologic study, urinalysis, and cystoscopy are important in the diagnosis of hemorrhagic cystitis, and these studies plus periodic excretory urography are important for surveillance. In addition, new methods of protecting against the urotoxicity are available.