AbstractThree mechanisms have been proposed for exposure of the conceptus to chemicals in semen: access of chemicals to the maternal circulation after absorption from the vagina, direct chemical exposure of the conceptus following transport from the vagina to the uterine cavity, and delivery to the egg and subsequent conceptus of chemical bound to the sperm cell. We review published data for each of these three mechanisms. Human seminal fluid chemical concentrations are typically similar to or lower than blood concentrations, although some antimicrobial agents achieve higher concentrations in semen than in blood. Vaginal absorption of medications has been shown to occur, although the vehicles in which these medications are delivered to the vagina may maintain contact with the vaginal epithelium to a greater extent than does semen. Assuming total absorption of a seminal dose of a chemical with a high semen:blood concentration ratio, distribution within the recipient woman would result in a blood concentration at least three orders of magnitude lower than that in the man. Direct delivery of seminal chemicals into the uterine cavity of humans has not been shown to occur, although it may occur in species such as the rat in which seminal fluid has access to the uterine cavity. Chemicals in or on human sperm cells have been demonstrated with respect to tetracycline and cocaine in vitro and aluminum, lead, and cadmium in vivo. The in vitro cocaine study offers sufficiently quantitative data with which to predict that oocyte concentrations would be five orders of magnitude lower than blood concentrations associated with cocaine abuse, assuming a maximally cocaine‐bound sperm were capable of fertilizing. Thus, even using liberal assumptions about transmission of chemicals in semen or sperm, predicted exposure levels of a pregnant woman or of the conceptus are three or more orders of magnitude lower than blood concentrations in the man whose semen is the putative vehicle for chemical transport. Birth Defects Res B 74:119–131, 2005. © 2005 Wiley‐Liss, Inc.