Recently, intense attention has been given to children's health issues, particularly in the use of consumer products. Because of this attention, researchers have been planning and initiating studies specifically aimed at developing both toxicology data and exposure data directed to improve our understanding of industrial and consumer product chemical impacts on children's health. To ensure that this research is focused on the highest priority chemicals, we present a methodology for determining and prioritizing the higher hazard chemicals and scenarios for which children could be disproportionately or highly exposed. This tiered approach includes a screening step for initial chemical selection, a hazard assessment based on no- or lowest-observed-adverse-effect levels, and a margin of exposure (MOE) calculation. The initial chemical screen focuses on the chemical presence in specific media that are special to children, such as foods children regularly eat and drink, residential or school air, products children use, and soil and dust in and around residences. Data from the literature or from models serve as the initial exposure estimate. This methodology would allow us to focus on those chemicals to which children are most exposed that are also associated with, potentially, the highest risk. Use of the MOE calculation allows for comparison among chemicals, prioritization of chemicals for evaluation and testing, and identification of significant data gaps.