Neuroleptic malignant syndrome (NMS) is an uncommon but serious adverse reaction to neuroleptic drugs. Clinically, it resembles malignant hyperthermia, a pharmacogenetic disorder of anesthesiology. Inv dup(15) is a rare but underrecognized cause of mental retardation among institutionalized patients. NMS and inv dup(15) have not been previously reported together. Their association should encourage clinicians to search for genetic markers for NMS.