To investigate the role of rat brain cortex Na+, K(+)-ATPase plasma membrane microenvironment in ethanol effect in vitro on membrane the sensitivity of enzyme activity to alcohol was studied under membrane perturbation induced by sodium dodecyl sulfate. The increase of enzyme sensitivity to detergent inactivation in the presence of high ethanol concentrations and to alcohol inhibition after modification by Ds-Na was revealed. It is supposed that Na+, K(+)-ATPase sensitivity to ethanol is dependent on structural state of protein microenvironment in accordance with assumed differences in structural organization of the boundary lipids of the neuronal enzyme isoforms.