Low-dose extrapolation model selection for evaluating the health effects of environmental pollutants is a key component of the risk assessment process. At a workshop held in Baltimore, MD, on April 23-24, 2007, and sponsored by U.S. Environmental Protection Agency and Johns Hopkins Risk Sciences and Public Policy Institute, a multidisciplinary group of experts reviewed the state of the science regarding low-dose extrapolation modeling and its application in environmental health risk assessments. Discussion topics were identified based on a literature review, which included examples for which human responses to ambient exposures have been extensively characterized for cancer and/or noncancer outcomes. Topics included: the need for formalized approaches and criteria to assess the evidence for mode of action; the use of human vs. animal data; the use of mode of action information in biologically-based models; and the implications of interindividual variability, background disease processes and background exposures in threshold vs. nonthreshold model choice.