The mitochondrial uncoupling protein-2 (UCP-2) is a recently discovered homologue of the brown adipose tissue-specific uncoupling protein and could be involved in the regulation of energy balance. Since obesity is associated with disturbed energy homeostasis, we tested the hypothesis that UCP-2 gene expression is deficient in this disorder. We determined, by a competitive reverse transcription-polymerase chain reaction assay, UCP-2 mRNA expression in intra- and extraperitoneal adipose tissues of 107 morbidly obese subjects and 31 lean control subjects. In both obese and non-obese subjects, UCP-2 mRNA abundance was higher in the intraperitoneal than in the extraperitoneal tissue (p < 0.05), but no association was observed between intra- and extraperitoneal expression in either group. Compared with lean control subjects, both male and female obese subjects displayed significantly lower average UCP-2 mRNA expression in the intraperitoneal adipose tissue (p < 0.006), while UCP-2 mRNA abundance in extraperitoneal adipose tissue was not different between obese and non-obese men and women. Intraperitoneal UCP-2 mRNA remained low in nine obese subjects who lost 23 +/- 12 kg of weight over a period of 10 +/- 5 months subsequent to weight reducing surgery. These data support the concept that impaired adipose tissue expression of UCP2 may play a role in the pathophysiology of obesity.