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Background: Susceptibility to lead toxicity is often assumed to be greatest during early childhood (e.g., 2 years of age), but recent studies suggest that blood lead concentrations (BPb) taken at 5-7 years of age are more strongly associated with IQ. Objective: We aimed to determine the age of greatest susceptibility to lead exposure using an innovative statistical approach that avoids the problem of correlated serial BPb measurements. Methods: We analyzed two cohorts of children that were followed from infancy to 6 years of age in Rochester, New York (n = 211), and Cincinnati, Ohio (n = 251). Serial BPb levels were measured and IQ tests were done when children were 6 years of age. After adjustment for relevant covariates, the ratio of 6-year BPb to 2-year BPb was added to the multiple regression model to test whether the pattern of BPb profiles during childhood had additional effect on IQ. Results: The ratio of BPb at 6 years to the BPb at 2 years showed a strong effect on IQ (p < 0.001) when added to the multiple regression model that included the average childhood BPb. IQ decreased by 7.0 points for children whose BPb at 6 years of age was 50% greater than that at 2 years compared with children whose 6-year BPb was 50% less than their 2-year BPb. Similarly, criminal arrest rates were a factor of 3.35 higher for those subjects whose 6-year BPb was 50% higher than their 2-year BPb. Conclusions: We conclude that 6-year BPb is more strongly associated with cognitive and behavioral development than is BPb measured in early childhood. [ABSTRACT FROM AUTHOR]