Increased concentrations of IL-1 and TNF have been associated with parturition. However, the role of these cytokines is unknown. Prior to parturition, the uterus undergoes a process of activation, during which there are significant changes in expression of genes associated with increased uterine contractility, including the receptors for oxytocin (OTR) and PGF₂ (FP), PG synthase isoform 2 (PGHS2), the gap junction protein connexin-43 (Cx-43) and the inducible isoform of nitric oxide synthase (iNOS). To determine if IL-1 or TNF were part of the causal mechanism for increased uterine contractions, we placed osmotic pumps infusing IL-1 or TNF into the peritoneal cavity of late pregnant rats (gestation day 19) and measured the effects on uterine contractility and on the uterine concentrations of mRNA for the contraction associated genes 24 hours later. Maternal serum concentrations of IL-1 and TNF were increased significantly. By day 21, the control animals had significant increases (P 0.05) in mRNA for OTR, FP, PGHS2 and Cx-43 and a decrease (P 0.05) in iNOS and an increase (P 0.05) in uterine sensitivity and responsiveness to oxytocin. Infusion of IL-1 or TNF had no effect on uterine contractility nor on expression of the activation associated genes. We conclude that intraperitoneal infusion of IL-1 or TNF resulting in significantly increased maternal serum cytokine levels does not cause uterine activation. The role of pro-inflammatory cytokines in the mechanism of parturition remains unclear.