In April, 1991 the Administrator of the U.S. Environmental Protection Agency (EPA) announced that the Agency would conduct a scientific reassessment of the risk of 2,3,7,8-tetrachlorodibenzo-p-dioxin (hereafter referred to as TCDD), and similar chemicals, to human health and the environment. Since 1985, EPA has classified TCDD, which it considers the most potent known animal carcinogen, as a probable human carcinogen. Sources of TCDD in the environment were subsequently regulated on the basis of animal cancer rates extrapolated to doses associated with human exposures. Recently, consensus has developed that the toxic effects of TCDD appear to be mediated by its binding to a receptor protein, the Ah cytosolic receptor. This conclusion has led to the supposition that a receptor-based model is appropriate for characterizing TCDD risk. As a consequence, EPA designed and implemented a reassessment research plan, founded on biologically-based dose-response models for TCDD and related chemicals, to establish a more scientific basis for credible risk assessments.