The effect of the alpha-2 adrenergic agonist clonidine on short-circuit current (SCC) across isolated skins of Bufo arenarum toads was investigated. 2. Clonidine inhibited basal SCC in a dose-dependent manner. 3. Blockade of the effect of clonidine on basal SCC by the selective alpha-2 antagonist yohimbine supports the hypothesis that the inhibitory effect is mediated by the stimulation of alpha-2 adrenergic receptors. 4. The fact that the inhibitory effect of clonidine is higher in skins with spontaneous positive SCC than in the negative ones, and that the alpha-2 agonist was unable to alter amiloride-induced negative SCC suggests that the inhibitory effect of clonidine may probably be mediated by inhibition of sodium transport.