Hemorrhagic cystitis is a common side effect of cyclophosphamide therapy not observed with other alkylating agents. In five patients receiving cyclophosphamide by mouth for prolonged periods with large cumulative dosage urinary-bladder tumors fatal to four and requiring cystectomy in the lone survivor developed. These observations strongly suggest chemical carcinogenicity of this drug in the production of these tumors. Increasingly, cyclophosphamide is being used for non-neoplastic disease. These circumstances suggest careful follow-up observation of patients in whom hemorrhagic cystitis from this drug develops for evidence of bladder cancer, as well as restraint in use of cyclophosphamide for non-neoplastic diseases if alternative therapy is available.