Chronic ethanol consumption has been shown to affect physical properties of membranes from animals as measured by electron spin resonance (ESR). This study compared for the first time the physical properties of erythrocyte membranes of alcoholic patients and control subjects using ESR procedures. Membrane fluidity was determined in the presence and absence of ethanol using the 5-doxyl stearic acid spin-label. Temperature-dependent phase transition also was determined, as were comparisons between ESR parameters, at the 1st and 5th week after alcohol withdrawal. Ethanol-induced fluidity was significantly greater in membranes of control subjects compared with alcoholic patients. Baseline fluidity did not differ and the temperature at which the phase transition occurred was not significantly different between the two groups. The resistance of membranes of alcoholic patients to fluidization by ethanol was unchanged after 5 weeks of withdrawal. Comparisons between ethanol-induced fluidization at the 1st and 5th week after withdrawal were not significantly different. These studies demonstrate differences in ethanol-induced fluidization between alcoholic patients and control subjects that are consistent with earlier ESR studies using an animal model.