Etomidate, an intravenous imidazole general anesthetic, is thought to produce anesthesia by modulating or activating ionotropic Cl^--permeable GABA_A receptors. Chromaffin cells are known to express functional GABA_A receptors with properties similar to their neuronal counterparts. We have shown that activation of the GABA_A receptors, with specific GABA_A agonists, leads to cellular excitation. Our goal was to determine whether etomidate mimicked this response and to explore the functional consequences of this activation. Imaging experiments with the Ca²⁺-indicator dye fura- 2 were used to assay [Ca²⁺]_i. Bovine adrenal chromaffin cells were superfused with a variety of GABA_A-selective drugs to determine their effects on [Ca²⁺]_i. Amperometric measurements were used to assay catecholamine release in real-time. We show that bovine adrenal chromaffin cells were excited by etomidate at clinically relevant concentrations. Etomidate directly activated GABA_A receptors found in chromaffin cells thereby elevating [Ca²⁺]_i. The effects of etomidate were mimicked by the specific GABA_A agonist muscimol and blocked by the specific antagonist bicuculline. Our data show that low concentrations of etomidate modulated GABA_A receptor activation by muscimol. Blockade of voltage dependent Ca²⁺ channels prevented the elevation of [Ca²⁺]_i by GABA. Application of etomidate directly to the chromaffin cells elicited robust catecholamine secretion from these cells. The data indicate that clinically relevant concentrations of etomidate can directly activate GABA_A receptors, which, due to the positive anion equilibrium potential, depolarizes chromaffin cells. This depolarization activates voltage-dependent Ca²⁺ channels thereby stimulating catecholamine release. Our data suggest that circulating catecholamine may be elevated after etomidate application.