Inward rectifier K+ channels (Kirs) were studied in the isolated perfused rat middle cerebral artery (MCA). The addition of 15 mM K+ (KCl) to the extraluminal bath dilated the MCAs. These dilations were blocked by selective inhibitors for the Kirs (40 microM BaCl2 or 40 mM CsCl) but not selective inhibitors for other K+ channels (glibenclamide, tetraethylammonium, or 4-aminopyridine). Neither removal of the endothelium nor treatment with the nitric oxide synthase inhibitor (NG-nitro-L-arginine methyl ester, 10 microM) affected the K(+)-induced dilation. The addition of BaCl2 to resting MCAs produced a dose-dependent constriction of 8-12%, indicating that, during resting conditions, Kirs aid in setting or determining the resting tone. The magnitude of the dilations produced by the addition of K+ or constrictions produced by BaCl2 were independent of pressure over a range of 40-100 mmHg. We conclude that Kirs, which produce a dilation when activated, exist on the vascular smooth muscle of the rat MCA. These Kirs aid in determining the resting tone of the vessel, and their function is independent of pressure over physiological pressure ranges.