Background. The toxicological assessment of the lipophilic persistent organic pollutants (POPs), including PCBs, pesticides and dioxins, is complicated since individuals are exposed to a complex mixture of contaminants. Therefore we developed ex vivo cell systems to determine the actual integrated level of xenobiotic activity in the human serum fraction containing the POPs. Sperm DNA integrity is essential for the accurate transmission of genetic information and sperm DNA damage can cause decreased male fertility. The AIM was to determine the integrated serum xenobiotic activity of POPs. The estrogen receptor (ER), androgen receptor (AR) and aryl hydrocarbon receptor (AhR) activity levels were compared among study groups from Greenland (53 adult males) and Europe (247 males from Sweden, Warsaw and Kharkiv) and further evaluated for association to the serum POP proxy markers 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) and 1,1-dichloro- 2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE) and sperm DNA. Results and Conclusions. No strong consistent correlations between serum xenobiotic activity and the two POP markers were found. However, using the sum of 14 PCBs and/or 10 organoclorine pesticides for analyses of Inuit data clear correlations were found. Thus, our data indicate that the selected POP markers alone can not predict the integrated serum xenobiotic activity. Significant different serum xenobiotic activities as well as levels of the POP proxy markers, DNA damage and %DFI were observed between Inuits and Europeans. For Inuits negative correlations between serum xenobiotic activities and DNA damage as well as %DFI were found, whereas for Europeans positive relations were seen. We suggest that the variation in serum xenobiotic activity reflects differences in POP exposure mixtures in context with genetic factors and/or life style factors. We believe that serum xenohormone activity can substantially contribute to the health assessment of chemical body burdens.