The ATP-sensitive K+ channel (KATP channel) and the Ca(2+)-activated K+ channel (KCa channel) were active in cell-attached and excised inside-out patch configurations in cultured smooth muscle cells of the porcine coronary artery. Vasopressin activated the KCa channel (240 pS) when it was applied in the bath in the cell-attached patch mode presumably because of an increase in intracellular Ca2+, but it had no direct effect on the KCa channel. However, vasopressin directly blocked the KATP channel from outside the cell membranes in a concentration-dependent manner in both outside-out and cell-attached patch configurations; the K(+)-channel opener, nicorandil, reversed this effect. The KATP channel (30 pS) was highly active in the intact cell-attached patch configuration when the pipette contained a physiological concentration of Ca2+, suggesting that this channel may control the resting membrane potential. (The block might produce depolarization of the cells and might result in the contraction of smooth muscle cells.) These observations suggest that the KATP channel may play a role, at least in part, in controlling the contraction of smooth muscle cells of the coronary artery and that the control of vascular tone by vasopressin may be related to its ability to block the KATP channel.