Neonatal sympathectomy with guanethidine (50 mg/kg for 3 wk) in Sprague-Dawley rats was previously shown not to significantly affect body weight gain, even when rats were raised in small litters and fed a high-calorie diet from weaning to produce diet-induced obesity (15). In our study rectal temperatures of cold-stressed (24 h at 4 degrees C) sympathectomized rats (obese and lean) fell only 1.4 degrees C after 4 h and were normal by 24 h, as were plasma catecholamine, glycerol glucose, and insulin levels after 4 h at 4 degrees C. Obese rats (with or without sympathectomy) had decreased 4-h (at 4 degrees C) plasma norepinephrine (NE) and increased basal and 4-h plasma glycerol, glucose, and insulin levels. Despite greater than 95% depletion of interscapular brown adipose tissue (IBAT) NE in sympathectomized rats, there was no alteration in beta-adrenoreceptor binding and only 10 and 32% decreases in basal and maximal NE-stimulated O2 consumption, respectively. Obese rats had significant increases in IBAT beta-receptor binding (148-190%/cell, 77-155%/pad) and in basal (11-19%) but not maximal O2 consumption. These results suggest that factors other than the sympathetic nervous system can effectively control thermoregulation, IBAT metabolism, and body weight in the presence of a chronic defect in sympathetic function.