We investigated the occurrence of hemorrhagic cystitis in 30 consecutive adult patients undergoing bone marrow transplantation (BMT) for hematological and non-hematological malignancies. Ten patients with hematological malignancies received allogeneic BMT, and twenty patients, seven with hematological and 13 with non-hematological malignancies, received autologous BMT. All 30 patients received high-dose cyclophosphamide-containing regimens (120 mg/kg in 16, 200 mg/kg in one, 6000 mg/m2 in 13) as preparative therapies. They all received 2-mercaptoethane sulphonate sodium (mesna) combined with hyperhydration 3 liter/day as prophylaxis for hemorrhagic cystitis. Bladder irrigation was not performed. Overall, five patients (16.7%) developed hemorrhagic cystitis; early-onset (within 48 hours of the end of the high dose chemoradiotherapy) hemorrhagic cystitis occurred in one (3.3%; 95% confidence interval, 0.6-16.7%) and late-onset occurred in four (13.3%; 95% confidence interval, 5.3-29.7%). In three of the four late-onset cases, adenovirus was isolated from the urine specimens at the onset of the hemorrhagic cystitis. Among the 13 patients with non-hematological malignancies receiving autologous BMT, one with recurrent breast cancer developed late-onset hemorrhagic cystitis associated with adenovirus type 11. We conclude the prophylactic measure with mesna and hyperhydration to be effective enough to prevent cyclophosphamide-induced hemorrhagic cystitis of early onset. Some BMT recipients, however, even those with non-hematological malignancies undergoing autologous BMT, develop late-onset hemorrhagic cystitis in which adenovirus is considered a principal causative agent.