The effect of peripheral administration of eledoisin on thyrotrophin-releasing hormone (TRH) and thyrotrophin (TSH) secretion in rats were studied. Eledoisin (500 micrograms/kg) was injected iv, and the rats were serially decapitated. TRH, TSH and thyroid hormone were measured by radioimmunoassay. The hypothalamic immunoreactive TRH (ir-TRH) content increased significantly after eledoisin injection, whereas its plasma concentration tended to decrease, but not significantly. Plasma TSH levels decreased significantly in a dose-related manner with a nadir at 40 min after the injection. Plasma thyroid hormone levels did not change significantly. Plasma ir-TRH and TSH responses to cold were inhibited by eledoisin, but the plasma TSH response to TRH was not affected. In the pimozide- or para-chlorophenylalanine-pretreated group, the inhibitory effect of eledoisin on TSH levels was prevented, but not in the L-dopa- or 5-hydroxytryptophan-pretreated group. These drugs alone did not affect plasma TSH levels at the dose used. The inactivation of TRH immunoreactivity by plasma or hypothalamus in vitro after eledoisin injection did not differ from that of controls. These findings suggest that eledoisin acts on the hypothalamus to inhibit TRH release, and its effects are modified by amines of the central nervous system.