The monosialoganglioside, GM1, protects the nervous system against a variety of insults. In this study, we evaluated the protective properties of GM1 on ethanol intoxication and development of dependence. GM1 (20-40 mg/kg, IP) reduced the extent and duration of ataxia produced by ethanol (2 g/kg, IP, 15-95 min), and delayed the onset of loss and reduced the duration of the righting reflex (LORR) produced by ethanol (4.2 g/kg, IP). GM1 did not alter ethanol-induced hypothermia or the rate of ethanol clearance. Rather, GM1 increased the waking blood ethanol concentration. In animals fed a complete liquid diet containing 4.5% ethanol, concurrent administration of GM1 (40 mg/kg/day) blocked the tremors, hypolocomotion, and anxiety-like behavior associated with ethanol withdrawal. These findings demonstrate that GM1 reduces both ethanol's acute intoxication and the signs and symptoms of ethanol withdrawal by a mechanism not related to ethanol pharmacokinetics.