BACKGROUND: Manganese is both an essential element and a known neurotoxicant to children. High manganese exposures have been associated with negative reproductive outcomes in animals, but few epidemiologic studies have examined the effects of human fetal manganese exposure. METHODS: We studied the association between maternal and umbilical cord blood manganese levels and birth weight in a cohort of 470 mother-infant pairs born at term (≥37 weeks gestation) in Ottawa County, Oklahoma. Nonlinear spline and quadratic regression models were used to test the hypothesis of an inverted U-shaped relationship between manganese levels and birth weight. RESULTS: Mean (standard deviation) concentration of manganese was 2.4 (0.95) μg/dL in the maternal blood and 4.2 (1.6) μg/dL in the cord blood. Umbilical cord manganese was not associated with birth weight. A nonlinear relationship was observed between maternal manganese and birth weight after adjusting for potential confounders. Birth weight increased with manganese levels up to 3.1 μg/L, and then a slight reduction in weight was observed at higher levels. Compared with the 3.1-μg/L point of inflection, birth weight estimates at the 5th (1.3 μg/L) and 95th (4.0 μg/L) percentiles of exposure were -160 g (95% confidence interval = -286 to -33) and -46 g (-38 to 131), respectively. CONCLUSIONS: Maternal blood manganese levels during pregnancy are associated with birth weight in a nonlinear pattern in full-term infants. These findings suggest that manganese may affect fetal growth. Possible detrimental effects of elevated manganese levels on the fetus should be further examined in more highly exposed populations.