Prolonged alcohol intake affects the morphology of the hippocampal formation of the rat and the resulting alterations do not reverse after withdrawal. Actually, an increase of the degenerative activity might occur in this condition. This unexpected observation prompted us to test the efficacy of neuronoprotective drugs during withdrawal. Because in a previous study we found that piracetam, a cyclic derivative of GABA, once added during withdrawal impedes hippocampal cell loss, we decided to evaluate the effect of this compound at the synaptic level. Using unbiased stereological techniques, we estimated the total number of contacts between mossy fibers and CA3 pyramids, as well as the volume and the surface area of the respective pre- and postsynaptic compartments. We found that in piracetam-treated withdrawn rats the number of synapses was higher than that observed in nonpiracetam-treated and alcohol-fed animals. The mechanisms leading to the synaptic reorganization took place at the mossy fiber level. The postsynaptic compartment does not seem to participate in the reorganization. It is suggested that the role of piracetam in this process might depend on the protective effect that this compound has upon glutamatergic receptors.