The neuroleptic malignant syndrome remains an intriguing syndrome, yet its pathogenesis is unknown. Despite numerous analogies with peripheral disorders of aberrant calcium migration in the sacroplasmic reticulum, the probable loci are striatal and hypothalamic (preoptic) dopaminergic pathways. In order to clarify the characteristics of dopamine activity, analysis of the central metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid in one case revealed marked elevations. A possible role for postsynaptic dopamine receptor inhibition is discussed. These findings further suggest that the syndrome may be similar to other extrapyramidal disorders, and they lend credence to observations of its reported drug induction and management.