The polychlorinated biphenyls (PCBs) constitute a group of persistent environmental chemicals including 209 possible congeners exhibiting a variety of chlorine substitution patterns. Due to their lipophilic nature and resistance toward biotransformation, PCBs accumulate in the food chain and all environmental matrixes including human adipose tissue, blood and milk. In most biological extracts PCB#138 (2,2',3,4,4',5-hexaCB), PCB#153 (2,2',4,4',5,5'-hexaCB), and PCB#180 (2,2',3,4,4',5,5'-heptaCB) are the dominating components. Depending on the position and number of chlorine substitutions, different classes of PCB congeners elicit a complex spectrum of biological and toxic responses in in vivo and in vitro models. Some PCBs exert dioxin-like activities mediated through the aryl hydrocarbon receptor (Ah receptor) giving rise to health risk such as organ toxicity and carcinogenesis. Although reports on interaction with other nuclear receptors are sparse, some congeners are hypothesized to possess endocrine disruptive potential through the Ah receptor and through interference with the biological activities of estrogens. Since most studies have been carried out using Aroclor technical mixtures, analysis of specific congeners are important to assess the risk in human exposure. Several pieces of evidence indicate that environmental chemicals, which are able to bind to the androgen receptor (AR) may have an important impact on abnormalities associated with the developing male reproductive system. An inhibition of the action of the AR during the embryonic stage may lead to alterations in the development of the male external genitalia such as cryptorchidism and hypospadia. Thus, environmental antiandrogens may have contributed to the increasing incidence of reproductive abnormalities observed in the human male population. The objective of the present study was to test the three PCBs which are most abundant in human breast milk (#138, #153, #180) for their ability to either agonize or antagonize the human androgen receptor (bAR) in a sensitive reporter gene assay. Comparison of these data to the potential Ah receptor activity of the PCBs was made.