1. Intravenous administration of 20-60 % glucose, 3.2-9.7 % NaCl or 20 % mannitol solutions (1.66 ml kg(-1)) for 5 min increased oxygen consumption in urethane-anaesthetized rats, whereas administration of physiological saline had no effect. Administration of 7.7-18.3 % urea slightly increased the oxygen consumption, but the increase was significantly smaller than that measured after the administration of other hypertonic solutions. The magnitude of the thermogenic effect correlated with the osmolality of the applied solutions. These results suggest that the thermogenesis was caused mainly by changes in osmolality rather than by a specific action of the different solute molecules. 2. Neither pretreatment with the ganglion blocker hexamethonium (20 mg kg(-1), I.P.) or the beta-adrenergic antagonist propranolol (10 mg kg(-1), I.P.), nor bilateral cervical vagotomy or bilateral adrenalectomy had any effect on the osmotically induced thermogenesis. Therefore, the autonomic nervous system and the adrenal gland were not involved in this metabolic response. 3. In response to osmotic stimulation, the temperature of the skeletal muscle increased significantly, whereas that of brown adipose tissue did not change and that of the colon and liver decreased. Accordingly, the site of osmotic thermogenesis is probably in the skeletal muscle, although osmotic stimulation was not accompanied by electromyographic activity and was not blocked by pretreatment with muscle relaxants such as dantrolene sodium or pancuronium bromide, or with the Na(+)-Cl(-) co-transport inhibitor bumetanide. 4. The increases in plasma osmolality observed after the administration of 20 % (1.3 osmol kg(-1)) glucose and 4.1 % (1.3 osmol kg(-1)) NaCl were 4.50 +/- 0.88 and 5.57 +/- 0.71 mosmol kg(-1), respectively. Since the slight increase in osmolality is well within the physiological range of changes that occur after food ingestion, diet-induced thermogenesis may have a component that is mediated by an increase in plasma osmolality, which results from the prandial increase in circulating nutrients.