The effects of somatostatin injections (0.1, 1 and 5 mug) into the paraventricular nucleus of the hypothalamus (PVN) were investigated in an open-circuit calorimeter. Wistar rats were tested, with no food available during the tests. The 0.1 and 1 mug doses produced large and long-lasting decreases in respiratory quotient, which indicates the preferential utilization of fats as an energy substrate. The 5 mug dose produced a brief decrease in energy expenditure. Locomotor activity was not affected by any treatment which indicates that the effects on respiratory quotient and energy expenditure are not secondary to changes in activity. These findings demonstrate that somatostatin in the PVN inhibits thermogenesis and induces the preferential utilization of fats while sparing carbohydrate reserves. However, it is significant that the effects on energy expenditure and energy substrate utilisation occurred at different doses. These data constitute the first evidence that somatostatin in the PVN produces a primary modulation of the metabolic parameters central to energy balance. In separate experiments, all three doses of somatostatin increased blood glucose concentration over a one hour period, and the 5 mug dose decreased body weight over a 24 h period. Food and water intake were not affected by the somatostatin injections. Taken together, these findings are interpreted in a model in which somatostatin is a signal to the PVN of increased body fat. This mobilises sympathetic mechanisms which increase fat utilization and blood glucose levels.