The major toxicity encountered with [131I]-Meta-iodobenzylguanidine (MIBG) therapy in neuroblastoma patients is an often isolated thrombocytopenia. We believe that this results from MIBG-induced radiotoxicity of the megakaryocytes. Since it is difficult to obtain enough human megakaryocytes for uptake studies, we investigated whether the megakaryocytic cell lines, MKPL-1, CHRF-288-11 and HEL, are good models to study serotonin and MIBG accumulation in human megakaryocytes. Compared with platelets, low levels of specific MIBG accumulation (imipramine-sensitive) were shown in all cell lines, but that of serotonin was negligible in MKPL-1 and CHRF-288-11. Furthermore, the proportion of specific uptake of both MIBG and serotonin appeared greatest in the HEL cells. Although these cells seem to be good candidates to study serotonin and MIBG uptake, they are not a good model to investigate MIBG and serotonin accumulation in human megakaryocytes since they have no functional storage granules.