Disturbed fat tissue metabolism with a reduction of the lipolytic rate could be an important pathogenetic factor in obesity. Lipolysis of the subcutaneous tissue of the thigh is partly under neural control and can be increased by intraneural stimulation of the lateral cutaneous femoral nerve in lean women. In the present study, we tested whether the lipolytic response to intraneural stimulation is altered in vivo in obese subjects. Seven obese women were examined and the results were compared with those of seven age-matched lean women. After an overnight fast, the lateral cutaneous femoral nerve was intraneurally stimulated for 10 min, and the local subcutaneous lipolytic response to this procedure was evaluated with microdialytic measurements of interstitial glycerol concentrations in the receptive field of the stimulated nerve fascicle. To exclude unspecific effects of stimulation, lipolysis was also controlled in a corresponding area of the contralateral leg. Intraneural stimulation produced no significant change in subcutaneous lipolysis in obese women (25.7 +/- 9.7%, NS). This finding is in sharp contrast with the marked regional lipolytic response in lean women in which the same stimulation procedure enhanced the regional interstitial glycerol levels by 72 +/- 17% (P < 0.05) compared with the unstimulated corresponding area of the contralateral leg. These in vivo results suggest that human obesity is characterized by a profound unresponsiveness of the subcutaneous adipose tissue to neurally stimulated lipolysis. This could be an important factor in the development and treatment of obesity.