Voltage-dependent potassium (Kv) channels have important functional roles in small arteries. We hypothesized that their interaction with caveolin-1 (Cav-1) contributes to the regulation of myogenic vasoconstriction in hamster gracilis arteries. Vascular responses were determined using videomicroscopy; Cav-1 function was reduced by transfection of a dominant-negative Cav-1 mutant. Cav-1-inhibited arteries exhibited less spontaneous (at 80mmHg) and pressure-induced (50 to 100mmHg) myogenic tone. Compared to controls, the amplitude of pressure-induced constriction was smaller following Cav-1 inhibition. Kv channel inhibitors (4-AP, XE991) augmented pressure-induced myogenic tone in both groups to a similar degree. Since the genetic deletion of Cav-1 has recently been shown to attenuate pressure-induced smooth muscle cell depolarization, our observations potentially indicate that Kv channels were activated in the transfected vessels. Our results add to the accumulating evidence that (i) the signalling elements that control the myogenic response are highly compartmentalized; and (ii) caveolae, organized by their structural protein Cav-1, provide the necessary microenvironment for these signalling elements.