This study had a dual purpose. First, the effects of pancreatic buffer flow on whole organ hormone output were investigated. Second, the receptor mechanisms by which sympathetic nerve stimulation alters the secretion rates of somatostatin and insulin were assessed. Pancreata of mongrel puppies were perfused in situ with nonrecirculated Krebs-Ringer bicarbonate buffer (150 mg/dl glucose). Buffer flow was adjusted between 0.2 and 4 ml/min X g pancreas. Insulin secretion rate (nanograms per min/g pancreas; ISR) as well as pancreatic O2 and glucose consumption increased as flow increased between 1 and 2 ml/min X g, where each reached a maximum plateau. Thus, ISR was shown to be dependent on flow over the middle range of flow investigated. In separate experiments, bilateral stimulation of the splanchnic nerves or pancreatic arterial infusion of norepinephrine to a final concentration of 60 microM decreased ISR and the somatostatin secretion rate (SSR). Adrenergic suppression of ISR was antagonized by phentolamine and phenoxybenzamine. Adrenergic inhibition of SSR was blocked only by phenoxybenzamine. Propranolol had no effects. We conclude that norepinephrine is sufficient to account for sympathetic inhibition of ISR and SSR (e.g. it is not necessary to postulate another transmitter) and that this inhibition may be transmitted through an effect on the islet vasculature or an effect on the islet cells themselves. The types of alpha-adrenoceptors mediating the adrenergically induced decrease in ISR differ from those causing the decrease in SSR.