A long-term prospective cohort study was conducted to examine the association between prenatal and postnatal exposure to environmental lead and childhood neuropsychological development. The possible interactive effects of blood lead and some covariates on early development were explored in this study. Our data suggest that gender of the child modifies the effect of lead on the neuropsychological development during early childhood. At the ages of 2 and 4 years, girls appear to be more sensitive than boys to the neuropsychological effects of lead. However, there is no significant modification of the effect of lead by some other covariates, such as parental smoking, socioeconomic status, home environment, birth weight, and the kind of infant feeding. Evidence of interactions between environmental lead exposure and other covariates in the causation of neuropsychological deficits in childhood underscores the desirability of considering both main effects and interactions in this area of research. Such effects, if confirmed, may have implications for public health intervention strategies.