In this study, we examined whether weight loss-induced changes in plasma organochlorine compounds (OC) were associated to those in skeletal muscle markers of glycolytic and oxidative metabolism. Vastus lateralis skeletal muscle enzyme activities and plasma OC (Aroclor 1260, PCB 153, p,p'-DDE, ß-HCH and HCB) were measured before and after a weight loss program in 17 men and 20 women. Both genders showed a similar reduction in body weight (~ 11 kg) in response to treatment, although men lost significantly more fat mass than women (P < 0.05). Enzymatic markers of glycolysis, phosphofructokinase (PFK) activity, and oxidative metabolism, beta-hydroxyacyl CoA dehydrogenase (HADH), citrate synthase (CS) and cytochrome c oxidase (COX) activities, remained unchanged after weight loss. Significant increase in plasma OC levels was observed in response to weight loss, an effect which was more pronounced in men. No relationship was observed between changes in OC and those in PFK activity in both genders (-0.31 < r < 0.10, NS). However, the greater the increase in plasma OC levels, the greater the reduction in oxidative enzyme (HADH, CS, COX) activities was in response to weight loss in men (-0.75 < r < -0.50, P < 0.05) but not in women (-0.33 < r < 0.33, NS). These results suggest that the weight loss-induced increase in plasma pollutant levels is likely to be associated with reduced skeletal muscle oxidative metabolism in men but not in women.