Intra-cerebroventricular (i.c.v.) injection of glucose (0.1-1.0 mumol) caused dose-dependent increases in resting oxygen consumption (Vo2) of conscious rats (maximum increase of 15.4 +/- 2% at 0.5 mumol). These effects were significantly attenuated by peripheral (i.p.) pretreatment with the beta-adrenoceptor propranolol, indicating the importance of the sympathetic nervous system (SNS) in the response. Plasma glucose concentrations were elevated (11%) 30 min after central injection of glucose, but intravenous glucose (0.5 mumol) did not affect resting Vo2. Animals which had been fasted for 12 h prior to Vo2 measurement exhibited reduced basal Vo2 values, but the nutritional state of the animal did not affect the metabolic response to central injections of glucose (0.5 mumol). Rats exhibiting genetic (fa/fa Zucker rats) and hypothalamic (VMH-lesioned) obesity showed similar thermogenic responses to centrally administered glucose, to their lean counterparts. These data suggest a dual action of central glucose in the regulation of energy balance, involving stimulation of energy expenditure in addition to its reported inhibition of energy intake. The defective diet-induced thermogenesis associated with VMH and genetic obesities does not appear to result from an inability to respond to changes in intracerebroventricular glucose concentrations.