Organochlorine compounds are released from body fat into the bloodstream during weight loss. Because these compounds may impair thyroid status, which is implicated in the control of resting metabolic rate (RMR), the aim of this study was to determine if the augmentation in plasma organochlorine concentrations might be associated with the decrease in serum T(3) concentration and RMR observed in response to body weight loss. Plasma organochlorine concentrations, serum T(3) concentration, and RMR were measured before and after weight loss in 16 obese men who followed a nonmacronutrient-specific energy-restricted diet for 15 weeks. As expected, a significant decrease in serum T(3) concentration and RMR was observed after the program, whereas concentrations of most detected organochlorines were significantly increased. Changes in organochlorine concentrations were negatively associated with changes in serum T(3) concentration (significantly for p,p'-DDT, HCB, Aroclor 1260, PCB 28, PCB 99, PCB 118, and PCB 170) and with changes in RMR adjusted for weight loss (significantly for HCB and PCB 156). In conclusion, organochlorines released in plasma during weight loss are associated with the documented decrease in serum T(3) concentration and RMR. Further studies are needed to verify whether these findings are causally related.