During human pregnancy the smooth muscle of the uterus, the myometrium, is relatively quiescent until the onset of contractile activity associated with labour. The cascade of events precipitating human labour remains unclear, but it is proposed that the myometrium becomes primed to contract at term by the activation of a complex array of genes encoding for proteins which include cyclo-oxygenase-II (COX-2), the oxytocin receptor and calcium regulatory proteins (TRPC isoforms and sarcoplasmic reticulum calcium ATPases). Several concordant stimuli (‘physiological’ inflammation, maternal and foetal endocrine signals and uterine stretch) have been implicated in this process and are proposed to drive the integration of uterine contractile activity and labour. In support of a central role for inflammatory cytokines, IL-1β, IL-8 and IL-6 have been found in myometrial tissue taken in late pregnancy, and raised concentrations are reported in amniotic fluid during human term and preterm labour. Experimental models of preterm labour have also demonstrated that introduction of bacterial products or cytokines into the amniotic cavity of pregnant animals leads to cytokine synthesis, up-regulation of Toll-like receptors and premature uterine contraction. This presentation will discuss how the inflammatory mediator IL-1β modulates uterine excitability. It is well known that that IL-1β can stimulate myometrial prostaglandin synthesis, but our studies demonstrate for the first time that IL-1β can also enhance calcium signalling events. IL-1β treatment of human myometrial cells induces spontaneous calcium oscillations and increases resting calcium concentrations in parallel with an augmentation of store-dependent calcium entry and a substantial increase in TRPC3 protein expression. Interestingly, IL-1β treatment does not alter expression patterns of any other TrpC isoforms suggesting that TRPC3 is differentially regulated. IL-1β-treated smooth muscle cells also exhibit augmented calcium responses to a diacylglycerol analogue (OAG), a prominent activator of TrpC3 channels. These data implicate TRPC3 channels as key mediators of the IL-1β enhancement of myometrial smooth muscle calcium signalling, and provide a plausible mechanism by which uterine excitability may be augmented in term and preterm labour. This cell model may also prove useful as an endogenous ‘overexpression’ system with which to explore the function, regulation and role of TrpC3 proteins. Acknowledgements: This work was supported by Tommy’s the baby charity (Reg. Charity No: 1060508) and The Wellcome Trust.