Recent advances in molecular and cellular biology allow for measurement of biologic events or substances that may provide markers of exposure, effect, or susceptibility in humans. The application of these new and emerging techniques to environmental health offers the possibility of significantly reducing the uncertainties that traditionally hamper risk assessments. The U.S. Environmental Protection Agency (EPA) health research program emphasizes the validation of appropriate biologic markers and their application to high-priority Agency issues. The rationale for EPA's biomarker research program is presented, and future research directions are discussed. Exposure biomarkers will receive most of the research emphasis in the near term, particularly body burden indicators of exposure to high-priority chemicals, such as benzene, ozone, selected heavy metals, and organophosphate pesticides. Research on effects biomarkers will attempt to validate the relationship between the observed biological effects and adverse health consequences in humans, especially for cancer, pulmonary toxicity, immunotoxicity, and reproductive/developmental toxicity.