Neuroleptic malignant syndrome (NMS) is a rare disorder characterized by hyperthermia, elevated creatine phosphokinase, extrapyramidal effects, autonomic instability, altered level of consciousness and leukocytosis associated with neuroleptic and other psychotropic medications. There are no cases of NMS reported following stem cell transplantation. We describe two patients receiving autotransplants who developed NMS. With the common use of neuroleptic and other related psychotropic medications in the peri-transplant period and the associated physiologic stress of the procedure, we believe that NMS may be unrecognized and account for significant morbidity in this setting.