The acute effects of alcohol involve inhibition of glutamatergic function, potentiation of GABA function, inhibition of calcium flow via voltage-operated calcium channels and increased dopamine release. With continued alcohol exposure adaptations, that appear to oppose the acute effects of alcohol, occur in each of these systems, which is the basis for tolerance. During chronic alcohol exposure the continued presence of alcohol through its acute effects opposes these adaptive changes and withdrawal symptoms are not evident. When alcohol is removed the adaptive changes are unopposed resulting in, increased excitatory glutamatergic function, decreased GABA inhibitory function, increased voltage-operated calcium channel function and decreased dopamine release. Thus the adaptive changes accounting for tolerance when unopposed by alcohol provide the neurobiologic basis of the alcohol withdrawal syndrome.