Stretch-activated ion currents were recorded from vascular smooth muscle (VSM) after enzymatic isolation of single cells from porcine coronary arterioles. Patch pipettes were used to record whole cell current and control cell length. Under voltage clamp in physiological saline solution, an inward cation current ( ICAT) was activated by 105–135% longitudinal stretch. ICATcoincided with an increase in intracellular Ca2+concentration. Under current clamp, membrane depolarization was induced by stretch. The magnitude of ICATvaried from −0.8 to −6.9 pA/pF at a holding potential of −60 mV. ICATwas graded with stretch, inactivated on release, and could be repeatedly induced. A potassium current ( IK) activated in unstretched cells by depolarization was also enhanced by stretch. In Ca2+-free bath solution, stretch-induced enhancement of IKwas blocked, but ICATwas still present. Hexamethyleneamiloride (50 μM), a reputed inhibitor of mechanosensitive channels, blocked ICATand the stretch-induced increase in IKbut not basal IK. Grammostolla spatulata venom (1:100,000) blocked basal IK, blocked stretch-induced increases in IK, and blocked ICAT. Iberiotoxin, a specific Ca2+-activated K+channel blocker, did not alter ICATbut blocked the stretch-induced increase in IKand increased the magnitude of stretch-induced depolarization. We concluded that longitudinal stretch directly activates a cation current and secondarily activates a Ca2+-activated K+current in isolated coronary myocytes. Although these two currents would partially counteract each other, the predominance of ICATat physiological potentials is likely to explain the depolarization and contraction observed in intact coronary VSM during pressure elevation.