Somatostatin (SS) is considered to be an important regulator of nutrient homeostasis. As such, we felt it would be of use to study in detail its effects on feeding. Intraperitoneal administration of SS (10 μg/kg) reduces spontaneous nocturnal feeding (3.6±0.6 g/2 hr vs 1.6±0.5 g/2 hr p < 0.025). In a separate study we found that SS also reduced spontaneous feeding in sham operated animals, but not in vagotomized animals (1.2±0.7 g/2 hr vs 3.8±0.3 g/2 hr, p < 0.05). SS inhibited stress (tail-pinch) induced eating at 10 and 1, but not 0.1 μg/kg and also inhibited insulin (10 U/kg) induced feeding over a 3 hour period at the 10 μg/kg dose. SS failed to inhibit feeding induced by either the intracerebroventricular administration of norepinephrine, the GABA agonist muscimol, or the endogenous opioid, dynorphin. SS (10 μg/kg) failed to suppress water intake or ingestion of a 2% sucrose solution suggesting that somatostatin does not suppress feeding by a generalized disruption of behavior or due to the aversiveness of SS. However, food intake also was not suppressed following food deprivation, suggesting a possible aversive effect of SS. We conclude that somatostatin may play a role as one of the physiological signals involved in short-term appetite regulation. Like CCK, the effects of SS would appear to be mediated through the vagus.