Weak, uncoordinated uterine contractions (labour dystocia) accounts for 20% of all caesarean sections (CS) in the UK. The only treatment available is application of oxytocin, which only works in 50% of cases. Lactate has been shown to be significantly increased in myometrial capillary blood during labour dystocia suggesting it may be impairing force production, but there are no functional data on the effect of lactate on the myometrium. We have therefore investigated its effect on contractility. Methods Myometrial strips were taken from term pregnant rats (22 day gestation) or biopsies obtained with written consent for women either not in labour (elective) or in labour, term CS. The effects on spontaneous contractility in response to sodium lactate (1-20 mM) and other weak acids: sodium butyrate, propionate and pyruvate (5-20 mM) were recorded. Oxytocin-stimulated contractions (0.1 nM rat, 0.5 nM human) were also investigated. In some experiments, tissue was loaded with Indo-1 AM to simultaneously measure force and intracellular Ca2+ signalling. Statistical differences were tested using non-parametric tests and significance taken as P<0.05. Results Lactate significantly decreased spontaneous contractility (n=6 rat, n=5 human). A dose dependent decrease in the integral of force (area under the curve, AUC) was seen, which was significant at concentrations of 5 mM (rat=36%±14%, human=44%±17%) and above (relative to control). Other weak acids also significantly reduced contractions in a dose dependent manner. The effects of lactate were significantly reduced in the presence of oxytocin (n=6 rat, n=4 human); 5mM lactate reduced AUC on oxytocin-driven contractions (rat=59% ± 15%, human=64% ± 15%, n=5). Because of this we determined the effects of lactate (5 mM) in biopsies from labouring myometrium. Significant reductions in force in the presence of oxytocin, were also found (amplitude, 81 ± 17 %, n= 6). Lactate inhibited Ca2+ transients and its effects on intracellular Ca2+ mirrored those of force (n=3). Conclusions Lactate in the physiological range potently decreases spontaneous contractility in both rat and human myometrium. The effects of lactate were influenced by physiological conditions, and while still significant, were reduced in the presence of oxytocin or labour. Other weak acids produce similar effects to lactate suggesting its mechanism of action is not via metabolism. Lactate inhibited Ca2+ transients, which could be due to a fall of intracellular pH. We suggest that differences in myometrial lactate production/efflux in women can lead to accumulation of extracellular lactate, which as we have shown, will reduce myometrial contractions and could therefore contribute to labour dystocia.