Stereotaxic microinjection of veratrine (50 micrograms in 1 microliter of saline) into the preoptic anterior hypothalamus of rats which were intraperitoneally pretreated with haloperidol (1 mg/kg), significantly elevated body temperature (1.4 degrees C above normal body temperature) and produced abnormal behaviors. This microinjection also facilitated turnover of dopamine and serotonin in the regions of the thalamus and hypothalamus. Hyperthermia induced by haloperidol plus veratrine was significantly inhibited by systemic administration of serotonin antagonists (cyproheptadine 10 mg/kg, ritanserin 3 mg/kg). These findings suggest that hyperthermia in neuroleptic malignant syndrome is due to the dominant effect of serotonin in the thermoregulatory center either by blocking the dopamine receptor or by enhancing the serotonin secretion.