Isoflurane, a halogenated volatile anesthetic, is thought to produce anesthesia by depressing central nervous system function. Many anesthetics, including isoflurane, are thought to modulate and/ or directly activate GABA_A receptors. Chromaffin cells are known to express functional GABA_A receptors. We have previously shown that activation of the GABA_A receptors, with specific agonists, leads to cellular excitation due to the depolarized anion equilibrium potential. In this study, our goal was to determine whether isoflurane mimicked this response and to explore the functional consequences of this activation. Furthermore, we wanted to study the actions of isoflurane on nicotinic ACh receptors (nAChRs) as they mediate the 'sympathetic drive' in these cells. For these studies the Ca²⁺-indicator dye fura-2 was used to assay [Ca²⁺]_i. Amperometric measurements were used to assay catecholamine release. We show that bovine adrenal chromaffin cells were excited by isoflurane at clinically relevant concentrations. Isoflurane directly activated GABA_A receptors found in chromaffin cells, which depolarized the cells and elevated [Ca²⁺]_i. Application of isoflurane directly to the chromaffin cells elicited catecholamine secretion from these cells. At the same time, isoflurane suppressed activation of nAChRs, which presumably blocks 'sympathetic drive' to the chromaffin cells. These latter results may help explain why isoflurane produces the hypotension observed clinically.