Previous studies demonstrated that alcohol induces marked deterioration of the cerebral cortex. However, quantitative evaluations of neurons and synapses of the prefrontal cortex from chronic alcohol-fed and withdrawn animals are nonexistent, in spite of the functional implications that can underlie structural changes in this cortical area. To achieve this evaluation, we used groups of rats alcohol-fed for 6, 12 and 18 months, their respective controls as well as groups of rats alcohol-fed for 6 and 12 months and then switched to water for 6 months--withdrawal groups. The thickness of the prelimbic cortical layers I-III was reduced in the alcohol-fed and withdrawal groups. A significant reduction in the density of cells was found, which was more marked after withdrawal. Conversely, the density of synapses increased after alcohol exposure and withdrawal; such numerical shifts lead to a significant increase in the synapse-to-neuron ratio. These results indicate that the cortical circuitry of the prelimbic cortex is vulnerable to prolonged periods of alcohol exposure and withdrawal and allow to advance the view that the alterations can induce functional implications.