We have investigated excitation-contraction coupling mechanisms associated with the activation of purinoceptors and putative pyrimidinoceptors by assessing the effects of ATP and UTP on cytoplasmic Ca<sup>2+</sup> activity ([Ca<sup>2+</sup>]<sub>i</sub>), membrane potential (E<sub>m</sub>) and force in rat mesenteric small arteries. UTP induced a sustained concentration-dependent contractions, closely associated with concentration-dependent increases in [Ca<sup>2+</sup>]<sub>i</sub>. Superfusion with 0.1 m M UTP caused a sustained depolarisation of 12 ± 1 mV (SE, n = 8). In Ca<sup>2+</sup>-free medium, the increase in [Ca<sup>2+</sup>]<sub>i</sub> and the contraction obtained with UTP (1 mM)were both transient and were inhibited by prior exposure to noradrenaline (NA). In vessels depolarised with KC1, UTP caused no change in E<sub>m</sub>, but a sustained increase in force and a transient increase in [Ca<sup>2+</sup>]i were induced, leading to an increased force/[Ca<sup>2+</sup>]<sub>i</sub> ratio. Similar effects on [Ca<sup>2+</sup>]<sub>i</sub>, E<sub>m</sub> and force were observed with ATP; but the effect of ATP on force was transient, whereas the effect on [Ca<sup>2+</sup>]<sub>i</sub> and E<sub>m</sub> declined only slowly. There was no cross-tachyphylaxis between the responses to ATP and UTP: in the presence of 1 m <X_Underline>M</X_Underline> of either, the other drug induced contractions in low concentrations, as if they acted through distinct receptors. The results suggest that both UTP and probably ATP release intracellular Ca<sup>2+</sup>, possibly from the stores emptied by NA. The sustained response to UTP appears to be due to an influx of extracellular Ca<sup>2+</sup>. UTP but not ATP was found to enhance the force-generating effect of [Ca<sup>2+</sup>]<sub>i</sub>.