The records of 314 children with acute lymphocytic leukemia (ALL) were reviewed to determine the frequency, clinical and laboratory features; contributing factors; and prognosis of cyclophosphamide-induced hemorrhagic cystitis. Twenty-five well-documented cases of hemorrhagic cystitis were identified. While most of the affected children suffered a mild transient illness, 1 patient died as a result of bladder hemorrhage. The doses of cyclophosphamide received by these children ranged widely and did not correlate with the severity of the cystitis. The frequency of this complication did not differ significantly with sex, age or route of administration. However, cystitis was over twice as frequent in black children as in white. Nineteen of 25 cases occurred in the spring and summer months. The group of affected children did not differ significantly from a matched control group in terms of total drug dosage received, incidence of systemic toxicity, mean urine specific gravity, or overall survival.