K+ dilate and constrict cerebral vessels in a dose-dependent fashion. Modest elevations of abluminal K+ cause vasodilatation, whereas larger extracellular K+ concentration ([K+]out) changes decrease cerebral blood flow. These dilations are believed to be mediated by opening of inward-rectifier potassium channels sensitive to Ba2+. Because BaCl2 also blocks ATP-sensitive K+ channels (KATP), we challenged K+ dilations in penetrating, resistance-size (<60 mμ) rat neocortical vessels with the KATP channel blocker glibenclamide (1 μM). Glibenclamide reduced K+ responses from 138 ± 8 to 110 ± 0.8%. K+ constrictions were not affected by glibenclamide. The Na+-K+-pump inhibitor ouabain (200 μM) did not significantly change resting vessel diameter but decreased K+ dilations (from 153 ± 9 to 99 ± 2%). BaCl2 blocked K+dilations with a half-maximal dissociation constant of 2.9 μM and reduced dilations to the specific KATP agonist pinacidil with equal potency. We conclude that, in resistance vessels, K+ dilations are mediated by KATP; we hypothesize that [K+]out causes activation of Na+-K+ pumps, depletion of intracellular ATP concentration, and subsequent opening of KATP. This latter hypothesis is supported by the blocking effect of ouabain.