The neuroleptic malignant syndrome (NMS) is a rare phenomenon that continues to generate controversy. By definition, for its diagnosis NMS requires exposure to drugs that alter dopaminergic function [i.e. neuroleptics (antipsychotics)]. The symptoms of NMS include hyperthermia, extrapyramidal side effects (EPS), altered mental status and autonomic dysfunction. Some investigators have viewed NMS as a variant of drug-induced hyperthermia, while others (including ourselves) have adopted the viewpoint that NMS is an extreme end of the spectrum of extrapyramidal disorders that can occur with fever. The true incidence of NMS is difficult to determine. The lack of established criteria for its diagnosis, by necessity, causes reports of incidence to vary. Young males appear to be more predisposed to NMS, but the reason for this is uncertain. There is some evidence to suggest that patients with organic brain disease may have a higher mortality rate. Cessation of treatment with neuroleptics should always occur in patients with severe NMS, i.e. where rigidity interferes with breathing, eating and drinking. Our treatment strategy involves treating the key elements of NMS - rigidity and elevated temperature. Initially, vigorous efforts should be made to reverse neuroleptic-induced rigidity with anticholinergics and intercurrent medical workup. If anticholinergics are ineffective (after up to 7 days' administration) bromocriptine is a rational substitute. After an episode of presumptive NMS, we recommend a 2-week period free of neuroleptics, followed by the use of an atypical neuroleptic such as clozapine or risperidone. The use of low dose neuroleptic regimens, atypical neuroleptics and concomitant use of benzodiazepines may significantly reduce the occurrence of NMS and potentially avoid this condition.-