In a fatal case of neuroleptic malignant syndrome, a muscle sample taken within 1 h of death showed acute myopathic features with absence of muscle glycogen and neutral lipid. These features suggest that hyperpyrexia in this syndrome may be caused by heat production from uncoupled phosphorylation in muscle and imply that the primary biochemical abnormality responsible for this uncontrolled heat production might be muscular rather than hypothalamic.