Infants and children are not little adults. They are uniquely vulnerable to environmental toxicants. To protect infants and children against toxicants, the National Research Council in 1993 called for development of an approach to risk assessment that considers children's unique patterns of exposure and their special vulnerabilities to pesticides. Many aspects of that call were codified into federal law in the Food Quality Protection Act (FQPA) of 1996. This report highlights the central elements needed for development of a child-protective approach to risk assessment: a) improved quantitative assessment of children's exposures at different life stages, from fetal life through adolescence, including acute and chronic exposures, exposures via multiple routes, and exposures to multiple agents; b) development of new approaches to toxicity testing of chemicals that can detect unanticipated and subtle outcomes and that evaluate experimental subjects over the entire life span from early exposure to natural death to replicate the human experience; c) development of new toxicodynamic and toxicokinetic models that account for the unique physiologic characteristics of infants and children; d) development of new approaches to assessment of outcomes, functional, organ, cellular and molecular, over the entire life span; these measures need to be incorporated into toxicity testing and into long-term prospective epidemiologic studies of children; and e) application of uncertainty and safety factors in risk assessment that specifically consider children's risks. Under FQPA, children are presumed more vulnerable to pesticides than adults unless evidence exists to the contrary. Uncertainty and safety factors that are protective of children must therefore be incorporated into risk assessment when data on developmental toxicity are lacking or when there is evidence of developmental toxicity. The adequate protection of children against toxic agents in the environment will require fundamental and far-reaching revisions of current approaches to toxicity testing and risk assessment.