Previous studies have demonstrated that pretreatment of rats with a GABA sub(A) receptor antagonist microinjected bilaterally into the preoptic area (POA) blocked cold- or lipopolysaccharide-induced thermogenesis. Here, the involvement of GABA sub(A) receptors in prostaglandin (PG)E sub(2)-induced fever was examined. Thermogenic, tachycardic, vasoconstrictive, and hyperthermic responses were elicited by the unilateral microinjection of 0.57-1.1 pmol PGE sub(2) into the region adjacent to the organum vasculosum of the lamina terminalis in urethane-chloralose-anesthetized rats. All these responses were blocked 10 min after pretreatment of the rats with a GABA sub(A) receptor antagonist, bicuculline methiodide or gabazine (50-500 pmol), microinjected unilaterally into the POA; and recovery occurred at ~70 min. Though the antagonist treatment alone had no effect on the O sub(2) consumption rate or colonic temperature, it did elicit a bradycardic response. Pretreatment with the vehicle, saline, had no effect on the PGE sub(2)-induced responses. However, the blocking action of bicuculline/gabazine was efficacious when the agent was administered unilaterally, but not necessarily bilaterally, into the POA either contralateral or ipsilateral to the PGE sub(2) injection site. These results suggest that the PGE sub(2)-induced responses are not simply mediated by the GABAergic transmission from the PGE sub(2)-sensitive site to the thermoefferent structure in the POA, although a tonic inhibitory input to POA neurons has a permissive role for the full expression of PGE sub(2)-induced fever.