The antagonism of depolarizing blockers, principally succinylcholine and decamethonium, by tetraethyl- and tetrabutylammonium ions in an in vivo neuromuscular preparation in anesthetized cats is described; possible mechanisms for these effects are discussed. Tetraethyl- (50-100 mg/kg, i.v.) and tetrabutylammonium (1-5 mg/kg, i.v.) produced sharp reversals of 95-99% succinylcholine and decamethonium blocks. These reversals were effective and sustained at any point during the course of the blockades. Tetraethyl- or tetrabutylammonium, administered 2-3 min before succinylcholine or decamethonium, prevented blockade, an effect compatible with an earlier reported in vitro investigation. The studies of others disclose the interaction of depolarizing blockers with acetylcholine receptors, leading to channel opening, channel entry and binding therein of these blockers. The present studies support this in showing the prevention of succinylcholine and decamethonium block by the prior administration of tetraethylammonium, which also interacts with acetylcholine receptors. It is proposed that a possible mechanism for tetraethylammonium reversals of succinylcholine and decamethonium blocks may be attributable to the tetraethylammonium reversal of a K+ current block by quaternary ammonium ions such as succinylcholine and decamethonium. Tetraethyl- and tetrabutylammonium ions proved to be effective antagonists of succinylcholine block following inactivation of plasma cholinesterases by hexafluorenium.