A high 24-h respiratory quotient (RQ), i.e., low fat oxidation, predicts weight gain. To determine whether impaired fat mobilization (lipolysis) may contribute to weight gain, we studied the relation between lipolytic response to nonselective -adrenergic stimulation and RQ measured in a respiratory chamber in 21 males (11 Caucasians, 10 Pima Indians; age 32 ± 5 yr, weight 93 ± 24 kg, body fat 30 ± 8%; means ± SD) and 23 females (10 Caucasians, 13 Pima Indians; age 32 ± 9 yr, weight 95 ± 26 kg, body fat 44 ± 8%). Lipolytic response was assessed as the relative increase in dialysate glycerol concentration (% above baseline) when isoproterenol (1 µmol/l) was added to the perfusate of a microdialysis probe inserted in the abdominal subcutaneous adipose tissue. In males, but not in females, basal RQ measured during sleep from 0500 to 0630 and adjusted for waist circumference was negatively correlated to lipolytic response (r = 0.66, P = 0.001). The results suggest that in males, impaired -adrenergic-mediated lipolysis may contribute to low rates of fat oxidation, a condition known to predispose to weight gain.