The Columbia Center for Children’s Environmental Health is using a combination of environmental and biologic measures to evaluate the effects of prenatal insecticide exposures among urban minorities in New York City. Of the 571 women enrolled, 85% report using some form of pest control during pregnancy and 46% report using exterminators, can sprays, and/or pest bombs. Chlorpyrifos, diazinon, and propoxur were detected in 99.7–100% of 48-h personal air samples collected from the mothers during pregnancy (n = 394) and in 39–70% of blood samples collected from the mothers (n = 326) and/or newborns (n = 341) at delivery. Maternal and newborn blood levels are similar and highly correlated (r = 0.4–08, P < 0.001). Levels of insecticides in blood samples and/or personal air samples decreased significantly following the 2000–2001 U.S. Environmental Protection Agency’s regulatory actions to phase out residential use of chlorpyrifos and diazinon. Among infants born prior to 1/1/01, birth weight decreased by 67.3 g (95% confidence interval (CI) −116.6 to −17.8, P = 0.008) and birth length decreased by 0.43 centimeters (95% CI, −0.73 to −0.14, P = 0.004) for each unit increase in log-transformed cord plasma chlorpyrifos levels. Combined measures of (ln)cord plasma chlorpyrifos and diazinon (adjusted for relative potency) were also inversely associated with birth weight and length (P ≤ 0.007). Birth weight averaged 215.1 g less (95% CI −384.7 to −45.5) among those with the highest exposures compared to those without detectable levels. No association was seen between birth weight and length and cord plasma chlorpyrifos or diazinon among newborns born after 1/1/01 (P > 0.8). Results support recent regulatory action to phase out residential uses of these insecticides.