Adrenergic receptor interaction with isoflurane was studied in anin vitrorat parotid gland model in which beta-adrenoceptor agonists evoke amylase release and alpha-adrenoceptor agonists induce potassium secretion from parotid cells. The amylase secretory studies were performed using a batch-incubation technique, and potassium efflux was evaluated using86Rb+as a probe for K+. Isoflurane was dissolved in a fat emulsion, which of its own had no secretory effect. Isoflurane induced a dose-dependent amylase release that was unaffected by beta-adrenergic blockade with propranolol and metoprolol. Isoflurane also induced a significant efflux of86Rb+that could not be inhibited by the alpha-adrenoceptor antagonist, phentolamine. Dinitrophenol, an uncoupler of oxidative phosphorylation, had no effect on the isoflurane-induced enzyme release, indicating that amylase secretion occurred by passive leakage. It is suggested that isoflurane has no direct action on alpha- or beta-adrenoceptors. Isoflurane, however, induces potent cellular events that might be due to an unspecific effect on the cell membrane, thereby causing changes in membrane permeability.