Hemorrhagic cystitis is a major cause of morbidity after bone marrow transplantation. Traditional methods of prevention have included mesna (2-mercaptoethane sodium sulfonate) and bladder irrigation. We report the use of hyperhydration as an alternative to these prophylactic measures. One hundred consecutive patients who underwent autologous or allogeneic bone marrow transplantation received high dose cyclophosphamide with hyperhydration using 5% dextrose normal saline at the rate of 250 ml/h and furosemide to maintain a urine output of >150 ml/h. Seventy-one of these patients also received high dose cyclophosphamide as mobilization chemotherapy. There were no episodes of hemorrhagic cystitis following mobilization chemotherapy. The incidence of hemorrhagic cystitis after transplant conditioning was 7% with 2 patients developing clinically significant hemorrhagic cystitis; one was a severe episode. The cost of hyperhydration was US$ 20 per course as opposed to US$ 1,500 per course for mesna, based on acquisition costs at our institution. We conclude that hyperhydration is a safe, inexpensive means of preventing hemorrhagic cystitis associated with high dose cyclophosphamide in bone marrow transplant recipients.