Manganese (Mn) is widely distributed in the biosphere but occurs in only trace amounts in animal tissues. Although Mn deficiency and toxicity both have pathological consequences, the underlying biochemical lesions have not been well defined. In vitro studies suggest that transport proteins are affected by Mn, lead (Pb), and selenium (Se). Among these transport proteins, the calmodulin-regulated calcium pump (Ca(2+)Mg(2+)ATPase) could be inhibited by Mn. In order to understand Mn biochemical pathways, we examined the relationships between Mn blood levels and red blood cell Ca-pump activity among 248 mothers and newborns, environmentally exposed to Mn, Pb, and Se. POPULATION AND METHODS: 248 mother-newborn pairs were recruited at Robert Debre University Hospital (Paris). Blood Mn and Pb concentrations were measured by absorption spectrophotometry. Se was measured by fluorometric method. Red blood cell membrane suspensions were obtained for Ca-pump activity measurements. Linear and quadratic regression models and Pearson correlation were performed. RESULTS: A non-linear parabolic relationship between maternal Mn blood levels and newborn Ca-pump activity was discovered from the analysis of the observed data. The peak level of maternal Mn that corresponded to a maximal activity of the newborn Ca-pump was estimated at 23.9 microg/l with a 95% confidence interval of 17.6 to 32.4 microg/l. An inhibition of this enzyme was observed at low and high levels of maternal Mn. The relationships between the newborn Ca-pump activity and maternal Se and Pb levels became non-significant after adjustment on all the co-factors included in the final model. CONCLUSION: Maternal environmental exposure to Mn, as reflected by maternal blood levels of this metal, is associated with a reduced activity of newborn erythrocyte Ca-pump in a non-linear pattern. Mn levels between 17.6 and 32.4 microg/l in maternal blood probably correspond to the optimal physiological concentration for the metabolism of this enzyme in newborns.