The effect of sympathetic nerve stimulation and intra-arterial infusion of neuropeptide Y (NPY) on net fluid secretion and release of vasoactive intestinal polypeptide (VIP) was studied in the cat small intestine during a secretion due to cholera toxin. Activation of the splanchnic nerves (4 Hz, 5 ms, 5 V) decreased net fluid secretion to 57 +/- 10% of control. Concomitantly, the release of VIP was reduced to less than 50%. Furthermore, close i.a. infusion of NPY (estimated increase in plasma concentration 75 nmol l-1) reduced the net fluid secretion and VIP release to 27 +/- 5 and 28 +/- 4% of the pre-stimulatory value. The correlation between the decrease in net fluid secretion and reduction in VIP release showed a strong positive correlation (r = 0.83). These results strongly indicate that the antisecretory effect of sympathetic nerve stimulation during cholera diarrhoea is mediated by inhibition of secretory VIP neurons in the intestinal mucosa. A similar mechanism is also proposed for the intravascularly administered NPY.