Challenging intact erythrocytes from normal human subjects with ethanol resulted in dose-dependent decreases in rates of acylation of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) while triacylglycerol (TAG) acylation was stimulated. In erythrocytes from alcoholic subjects, the responses were of lesser magnitude, indicating a lower sensitivity to ethanol. This in vitro resistance, typical of the state of tolerance, was associated in erythrocytes from alcoholic subjects with increased baseline rates of acylation of PC, PE and TAG, suggesting high levels of glycerolipid fatty acid turnover. These results suggest that (1) intact human erythrocytes are qualitatively and quantitatively valid for studying the adaptive response to ethanol; and (2) chronic alcoholism is associated with increases in turnover rates of the acyl moieties of lipid membrane components regardless of the pattern of initial sensitivity to ethanol. Increased acylation rates during chronic alcoholism might modify the remodeling of the lipid matrix and thereby the membrane function.