Mechanisms underlying the decreased febrile response in the elderly have not been elucidated. One hypothesis is that elderly persons have a decreased response at the hypothalamic or peripheral effector level to endogenous pyrogen (EP). We studied the response to human monocyte-derived EP in young adult and aged Fischer 344 rats, a strain known to have an age-dependent decrease in the febrile response to endotoxin. EP was given intraperi-toneally to aged and young adult rats kept at 26°C (thermoneutral zone) or at 15°C (a mild cold stress), in order to accentuate possible peripheral thermoeffector defects. At 26°C, the febrile response in aged rats was similar to that in young adult rats. At 15°C, the febrile response was lower in both groups, but the aged rats did not differ from the young adult rats. When EP was given by intracerebroventricular injection to aged and young adult rats, at 26 or at 15°C, no differences in the febrile responses were noted. Thus, it appears that in aged Fischer rats the hypothalamic response and the peripheral effector response to EP are intact. Further studies on the production and release of EP by rat monocytes are needed to explain the diminished febrile response to endotoxin in the aged