Free fatty acids (FFA) and fatty-acid ethyl esters (FAEE) were extracted from different organs of rat after ethanol administration. The results showed that ethanol treatment increased the concentration of saturated and mono-unsaturated FFA and FAEE while decreasing the poly-unsaturated fatty-acid content. Pretreatment of animals with Metadoxine one hour before ethanol administration inhibited the increased formation of saturated and mono-unsaturated FFA. While ethanol administration induced a marked increase in glutathione (GSH) S-transferase activity correlated with increased formation of FAEE in different rat tissues examined, pretreatment of such rats with Metadoxine reduced considerably the increased enzyme activity of their GSH S-transferase. Elevated concentrations of saturated and mono-unsaturated FFA conceivably reflect changes in the composition of lipid membranes. Hence, the cellular response to ethanol would be the formation of highly-packed rigid membrane structures. Pretreatment with Metadoxine causes an inhibition in the formation of elevated quantities of saturated and mono-unsaturated fatty acids. This condition could result in a lower degree of adaptability to ethanol intake and perhaps a decreased level of tolerance to ethanol.