Biologic markers have been discussed extensively in the scientific literature in the past 5 years. That literature generally has focused on the promise and limitations of markers. Currently, a great amount of effort is under way in government, academia, and the private sector to move the field forward. This effort may be characterized by the inventory and review of potential markers and their use. The next requirement is to add a consideration of research and design strategies for the validation and use of biologic markers, especially as they pertain to the assessment of xenobiotic exposures and resultant health impairments. This paper delineates a conceptual framework for the validation and use of biologic markers. It expands on the concept of a continuum of events between ambient exposure to a xenobiotic substance and resultant clinical disease. Strategies for research and marker validation are presented. Biologic markers are considered useful in etiologic and mechanistic research, in secondary prevention of disease, in risk assessment, and in assessing the effectiveness of environmental controls.