A Phase I trial of irinotecan hydrochloride (CPT-11) was performed to determine the maximum tolerated dose (MTD), the dose-limiting toxicities, and the incidence and severity of other toxicities in children with advanced neuroblastoma. Three children received 11 courses of CPT-11 administered as a 90-min i.v. infusion, daily for 3 days every 21 days. Doses ranged from 100 mg/m2 to 220 mg/m2. Two peaks in the total number of instances of diarrhea was observed, 25 stools at 3 days and 32 stools at 10 days. Myelosuppression was well controlled and of brief duration. One child achieved a clinical complete response (CR) and 2 had a partial response (PR). The MTD of CPT-11 administration was 180 mg/m2 for 3 days. These results indicate the usefulness of CPT-11 for the treatment of advanced neuroblastoma. Further investigation is necessary to establish its role in combination chemotherapeutic regimens.