Strains of mouse (Swiss OF 1, DBA/2J Ico and C57 BL/6J Ico) with different sensitivities to the hypnotic effects of acute ethanol administration were also found to have differences in fatty acid composition in synaptosomal and erythrocyte membrane phospholipids. Chronic ethanol treatment altered membrane fatty acid composition in quantitatively different ways depending on whether the mice developed tolerance (DBA, C57) or not (Swiss). These results support the hypothesis that membrane lipid composition plays a role in the sensitivity to the effects of ethanol.