Rats have an attenuated febrile response to intraperitoneal (i.p.) administration of exogenous pyrogen (e.g. bacterial endotoxin) near the term of pregnancy. To investigate possible mechanisms of this unique thermoregulatory response, the present experiments were carried out on 18 non-pregnant and 16 near-term pregnant Sprague-Dawley rats to test the hypothesis that pregnancy alters the balance of pyrogenic cytokines and antipyretic and/or cryogenic (antipyretic/cryogenic) cytokines in response to exogenous pyrogen. To test our hypothesis, we measured plasma levels of interleukin (IL)-1beta, IL-6, interleukin-1 receptor antagonist (IL-1ra) and tumour necrosis factor alpha(TNFalpha) at 2 and 4 h following i.p. administration of 160 microg kg(-1) E. coli lipopolysaccharide (LPS) (i.e. EC100 dose, or the smallest dose that elicits a maximal febrile response in non-pregnant rats) in non-pregnant as well as pregnant rats at day 20 of gestation (term approximately 21 days). In non-pregnant rats, E. coli LPS elicited statistically significant increases in plasma concentrations of IL-1beta, IL-6, IL-1ra and TNFalpha as compared to that observed following administration of vehicle. However in pregnant rats, E. coli LPS elicited statistically significant increases in antipyretic/cryogenic cytokines (IL-1ra and TNFalpha) but not in pyrogenic cytokines (IL-1beta and IL-6). Thus, a differential pyrogenic and antipyretic/cryogenic plasma cytokine response may mediate in part the attenuated febrile response to exogenous pyrogen observed in rats near the term of pregnancy.