n-Hexacosanol, a long-chain saturated fatty alcohol extracted from Hygrophyla erecta Hochr., has been recently shown to exert neurotrophic properties on central neurons and to stimulate phagocytosis in macrophages. The present work was designed to investigate the effects of hexacosanol on stimulated insulin secretion in vivo and in vitro. In anaesthetized rats, hexacosanol (2 mg/kg i.p.) induced a reduction of the insulin response to an intravenous glucose tolerance test (0.3 g/kg) with a consequent increase in hyperglycaemia. In vitro, in the isolated perfused pancreas, hexacosanol at the concentration of 10(-7) M clearly reduced the two phases of glucose-induced insulin secretion. At the higher concentration (10(-5) M), hexacosanol was no longer able to exert an inhibition of glucose-induced insulin release; surprisingly a stimulating effect occurred which was of the same magnitude as in control experiments with Tween alone, at the concentration used to dissolve hexacosanol. In isolated perifused islets, 22 mM glucose-stimulated insulin release was also inhibited by hexacosanol at the concentrations of 10(-9) M and 10(-7) M, but not at 10(-5) M. In contrast, insulin secretion induced by arginine (20 mM) was not affected by the different concentrations of hexacosanol. It is concluded that n-hexacosanol at 10(-9) M and 10(-7) M exerts an inhibitory effect on insulin secretion stimulated by glucose in vivo and in vitro in the rat, suggesting a direct effect on islets of Langerhans.