Trichloroacetaldehyde monohydrate [chloral hydrate (CH)] is a sedative/hypnotic that increases cerebral blood flow (CBF), and its active metabolite 2,2,2-trichloroethanol (TCE) is an agonist for the nonclassical two-pore domain K ϩ (K 2P ) channels TREK-1 and TRAAK. We sought to determine whether TCE dilates cerebral arteries in vitro by activating nonclassical K ϩ channels. TCE dilated pressurized and perfused rat middle cerebral arteries (MCAs) in a manner consistent with activation of nonclassical K ϩ channels. Dilation to TCE was inhibited by elevated external K ϩ but not by an inhibitory cocktail (IC) of classical K ϩ channel blockers. Patch-clamp electrophysiology revealed that, in the presence of the IC, TCE increased wholecell currents and hyperpolarized the membrane potential of isolated MCA smooth muscle cells. Heating increased TCEsensitive currents, indicating that the activated channel was thermosensitive. Immunofluorescence in sections of the rat MCA demonstrated that, like TREK-1, TRAAK is expressed in the smooth muscle of cerebral arteries. Isoflurane did not, however, dilate the MCA, suggesting that TREK-1 was not functional. These data indicate that TCE activated a nonclassical K ϩ channel with the characteristics of TRAAK in rat MCA smooth-muscle cells. Stimulation of K ϩ channels such as TRAAK in cerebral arteries may therefore explain in part how CH/TCE increases CBF.