Perfusion of the rat mesenteric bed with 0.1 or 10 nM neuropeptide Y potentiated the noradrenaline-induced increase in mesenteric pressure; the peptide did not modify basal perfusion pressure. While perfusion with 0.1 nM neuropeptide Y significantly increased the maximal noradrenaline-evoked vasoconstriction without modifying its EC50, 10 nM neuropeptide Y potentiated the maximal noradrenaline effect and significantly shifted its concentration-response curve to the left. Perfusion with 1-10 microM D-myo-inositol 1,2,6-trisphosphate (alpha-trinositol) reduced, in a concentration-dependent fashion, the neuropeptide Y-induced potentiation of the noradrenaline-evoked vasoconstriction without altering the potency or maximal response evoked by the catecholamine alone. Perfusion with 0.1 nM neuropeptide Y plus 1 microM alpha-trinositol completely abolished the neuropeptide Y-induced facilitation of the noradrenaline effect. alpha-Trinositol 1 microM in the presence of 10 nM neuropeptide Y caused a nonparallel rightward shift of the noradrenaline concentration-response curve as compared to that obtained in the presence of 10 nM neuropeptide Y alone. The alpha-trinositol blockade of the facilitatory action of neuropeptide Y was reversible.