Guinea pigs with anteroventral third ventricle region (AV3V) lesions fail to develop fever and the associated rise in acute-phase plasma protein levels following systemic injections of lipopolysaccharide (LPS). Since endogenous pyrogen (EP) injected directly into the preoptic area of animals with AV3V lesions causes appropriate elevations in core temperature (Tco) and acute-phase plasma proteins levels, the blocked responses to LPS probably are not due to damage to the adjacent preoptic area. We proposed, therefore, that EP may pass from blood into brain in the AV3V, presumably through the organum vasculosum laminae terminalis. However, the possibility that a more generalized impairment due to damaged pathways within the AV3V could account for the observed effects was not examined. To investigate this possibility, guinea pigs were given AV3V lesions. Pending histological verification of the ablated sites, AV3V lesions were presumed to be placed correctly if the animals did not develop fever following LPS (Salmonella enteritidis, 2 micrograms/kg i.p., at ambient temperature (Ta) 22 degrees C); those failing to meet this criterion were designated as sham-operated. Two experiments were conducted. In the first, metabolic rates, Tco, and two skin temperatures (Tsk) were measured at Ta 12 degrees, 22 degrees, and 32 degrees C over an 8-month postlesion period during which failure to fever persisted; the data were collected during a 30-min period after thermal balance had been achieved at any given Ta. There were no differences in the variables measured between sham-operated and AV3V-lesioned animals at Ta 22 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)