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A captive study was performed with Greenland sledge dogs (Canis familiaris) fed a naturally organohalogen-contaminated diet (Greenland minke whale [Balaenoptera acutorostrata] blubber; exposed group) or a control diet (pork fat; control group). The catalytic activity of major xenobiotic-metabolizing phase I and II hepatic microsomal enzymes was assessed. Relative to control dogs, ethoxyresorufin-O-deethylase (EROD) activity in exposed dogs was twofold higher (p = 0.001). Testosterone hydroxylation yielded 6beta- and 16beta-hydroxy (OH) testosterone and androstenedione, with higher rates of production (23-27%; p < or = 0.03) in the exposed individuals. In the exposed dogs, epoxide hydrolase (EH) activity was 31% higher (p = 0.02) relative to the control dogs, whereas uridine diphosphoglucuronosyl transferase (UDPGT) activity was not different (p = 0.62). When the exposed and control dogs were combined, the summed (sigma) plasma concentrations of OH-polychlorinated biphenyl (PCB) congeners were predicted by plasma sigmaPCB concentrations and EROD activity (p < or = 0.04), whereas testosterone hydroxylase, EH, and UDPGT activities were not significant predictors of these concentrations. Consistent results were found for individual OH-PCB congeners and their theoretical precursor PCBs (e.g., 4-OH-CB-187 and CB-183, and 4-OH-CB-146 and CB-146) and for EROD activity. No association was found between sigmaOH-polybrominated diphenyl ether (PBDE) and sigmaPBDE plasma concentrations, or between potential precursor-metabolite pairs, and the enzyme activities. The present results suggest that liver microsomal EROD activity and plasma PCB concentrations have a greater (e.g., relative to EH activity) predictive power for the occurrence of plasma OH-PCB residues in sledge dogs. These results also suggest that plasma OH-PBDEs likely are not products of cytochrome P450-mediated transformation but, rather, are accumulated via the diet.