The US Environmental Protection Agency (EPA) has released the first part of its long-awaited dioxin reassessment. The document is the first of two EPA reports that, together, will respond to the recommendations and comments on 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) dose-response assessment included in the 2006 NAS report, Health Risks from Dioxin and Related Compounds: Evaluation of the EPA Reassessment. The released document, Reanalysis Volume 1, includes (1) a systematic evaluation of the peer-reviewed epidemiologic studies and rodent bioassays relevant to TCDD dose-response analysis; (2) dose-response analyses using a TCDD physiologically based pharmacokinetic model that simulates TCDD blood concentrations following oral intake; and (3) an oral reference dose (RfD) for TCDD. An RfD of 7 × 10-10 mg/kg-day is derived based on two epidemiologic studies: (a) a study that associated TCDD exposures with decreased sperm concentration and sperm motility in men who were exposed during childhood and (b) a study that associated increased thyroid-stimulating hormone levels in newborn infants born to mothers who were exposed to TCDD. A qualitative discussion of uncertainties in the RfD and a focused quantitative uncertainty analysis of the choices made in the development of points of departure for RfD derivation are also provided.