Ethanol disrupts the physical structure of cell membranes. The most fluid membranes, including those that are low in cholesterol, are the most easily disordered by ethanol. Although the membrane-disordering effect is small, there is pharmacological, temporal, and genetic evidence that it is important. Animals that are resistant to ethanol intoxication because of their genetic background or because of previous exposure to ethanol are found to have brain membranes that are not easily disordered in vitro. An exception is the increased behavioral sensitivity in aging animals, which is not matched by changes in their membranes. When animals are treated chronically with ethanol, their membranes become stiffer, a response that can be regarded as adaptive. Ethanol may favor the uptake of cholesterol or saturated fatty acids into membranes, thus reducing its own effect.