© 2015 Cancer Research UK. Background: 131 I-metaiodobenzylguanidine (MIBG) is an active radiopharmaceutical in neuroblastoma. A previous study demonstrated that MIBG could be combined with vincristine and prolonged irinotecan, although 25% of first courses had grade 3 diarrhoea. The current phase I/II study evaluated MIBG with vincristine and 5 days of higher-dose irinotecan.Methods:Patients 1-30 years old with advanced neuroblastoma were eligible. Patients received cefixime on days -1 to +6, irinotecan (50 mg m -2 per dose IV) on days 0-4, vincristine (2 mg m -2) on day 0, MIBG (555 or 666 MBq kg -1) on day 1, and peripheral blood stem cells on day 13. UGT1A1 genotyping was performed in consenting patients.Results:Thirty-two patients (12 phase I; 20 phase II) received 42 courses. No dose-limiting toxicities were seen during dose escalation and the recommended administered activity was 666 MBq kg -1. Myelosuppression and diarrhoea were the most common toxicities, with grade 3 diarrhoea in 6% of first courses. Patients homozygous for UGT1A1∗28 had more grade 4 thrombocytopenia (80% vs 37%; P=0.14). Responses (five complete and four partial) occurred in 9 out of 32 (28%) patients.Conclusions:MIBG (666 MBq kg -1) with vincristine and this irinotecan schedule is tolerable and active, with less severe diarrhoea compared with a regimen using more protracted irinotecan.