In urban areas with a predominance of early to mid-20th century housing stock, islands of children possessing blood lead levels (PbB) in excess of CDC guidelines (>10 μg/dL) exist. Many of these children are also exposed to environmental tobacco smoke (ETS). The current study examined the impact of Pb-exposure (PbB levels of 1-55 μg/dL) with/without concurrent ETS exposure on immune system function in 318 children aged 6-84 months from the urban area of Springfield-Greene County, Missouri. In this population, 36.5% of children possessed PbB levels >10 μg/dL, 62.9% of children came from smoking homes, 51.9% of children were under 2 years of age, and the population was WIC eligible and predominantly of white, non-Hispanic ethnicity. Multiple immune function markers including cell counts, IgE levels, sCD25 (sIL2R) and IL4 concentrations, and titers to common childhood immunizations were analyzed for correlation with Pb and/or ETS exposure. Increased IgE levels (p<0.01) were found in children with PbB levels within CDC Classes II-IV—this finding was primarily attributable to elevated IgE levels in the subpopulation of children with concurrent Pb and ETS exposure. A trend (0.05