Background: Recent evidence suggests that low-level environmental exposure to manganese adversely affects child growth and neurodevelopment. Previous studies have addressed the effects of prenatal exposure, but little is known about developmental effects of early postnatal exposure. Methods: We studied 448 children born in Mexico City from 1997 through 2000, using a longitudinal study to investigate neurotoxic effects of early-life manganese exposure. Archived blood samples, collected from children at 12 and 24 months of age, were analyzed for manganese levels using inductively coupled plasma mass spectrometry. Mental and psychomotor development were scored using Bayley Scales of Infant Development at 6-month intervals between 12 and 36 months of age. Results: At 12 months of age, the mean (SD) blood manganese level was 24.3 (4.5) μg/L and the median was 23.7 μg/L; at 24 months, these values were 21.1 (6.2) μg/L and 20.3 μg/L, respectively. Twelve-and 24-month manganese concentrations were correlated (Spearman correlation = 0.55) and levels declined over time (β =-5.7 [95% CI =-6.2 to-5.1]). We observed an inverted U-shaped association between 12-month blood manganese and concurrent mental development scores (compared with the middle 3 manganese quintiles, for the lowest manganese quintile, β =-3.3 [-6.0 to-0.7] and for the highest manganese quintile, β =-2.8 [-5.5 to-0.2]). This 12-month manganese effect was apparent but diminished with mental development scores at later ages. The 24-month manganese levels were not associated with neurodevelopment. Conclusions: These results suggest a possible biphasic dose-response relationship between early-life manganese exposure at lower exposure levels and infant neurodevelopment. The data are consistent with manganese as both an essential nutrient and a toxicant.