The hypothesis that neuropeptide Y (NPY) potentiates noradrenaline (NA)-induced vascular force development by increasing free intracellular Ca<sup>2+</sup> ([Ca<sup>2+</sup>]<sub>i</sub>) was tested in rat mesenteric resistance arteries. NPY (100 n M) alone was not able to increase either the contraction or [Ca<sup>2+</sup>]<sub>i</sub>. However, pretreatment of mesenteric resistance arteries with 100 n M NPY potentiated both [Ca<sup>2+</sup>]<sub>i</sub> and active stress induced by 1.5 µ M NA. Addition of 100 n M NPY to vessels that had been precontracted with NA (1.5 µ M) elicited a large increase in [Ca<sup>2+</sup>]<sub>i</sub> and an increase in active stress development. In Ca<sup>2+</sup>-free medium containing 2 m M ethylene glycol-bis(β-aminoethyl ether) NNN’N’-tetraacetic acid, the potentiating effect of NPY on the NA-induced contraction was prevented, and readdition of Ca<sup>2+</sup> resulted in a large increase in both [Ca<sup>2+</sup>]<sub>i</sub> and active stress development. It is concluded that NPY potentiates NA-induced contraction in the isolated mesenteric resistance artery by inducing a rise in [Ca<sup>2+</sup>]<sub>i</sub> through an influx of Ca<sup>2</sup> from the extracellular source.