Alpha adrenergic stimulation elicits a rapid release of K+ from dispersed rat parotid cells. Surprisingly neither clonidine, oxymetazoline, naphazoline, ST 600 nor ST 91 elicited K+ release from parotid cells at concentrations up to 100 micrometer. By contrast, these agents were able to block epinephrine-stimulated K+ release with the relative potencies: oxymetazoline more than naphazoline more than clonidine more than ST 600 more than ST 91. [3H]-Dihydroergocryptine (DHE) binds to sites on parotid membranes and intact dispersed cells with the characteristics of alpha adrenergic membrane receptors. The ability of these imidazolines to displace [3H]DHE binding from parotid membranes correlated with their potencies as alpha adrenergic antagonists in the dispersed cells. Although clonidine, oxymetazolin and naphazoline are agonists in other peripheral alpha adrenergic receptors, they are antagonists in the parotid. This observation explains the most common side-effect of clonidine administration, dry mouth, and is consistent with the proposition that different groups of alpha adrenergic receptors exist in mammalian tissues. These data also suggest that the central actions of clonidine must be interpreted with caution since alpha adrenergic receptors similar to those in the parotid may be present in brain.