The isolation of subfractions of cell membranes on the basis of their solubility in non-ionic detergents has led to the discovery of lipid domain structure in membranes. Detergents used for this purpose include Triton, Brij, Lubrol and CHAPS. Different lipid constituents are known to resist solubilization by different detergents and the resulting fractions may associate with different membrane proteins. In general, the detergent-resistant membrane fractions tend to be dominated by saturated molecular species of sphingomyelin and phosphatidylcholine and invariably include significant proportions of cholesterol. The lipid composition is consistent with formation of liquid-ordered phases. The present evidence favours a model in which the lateral segregation of membrane proteins takes place on the basis of their affinity for liquid-ordered lipid domains within the membrane.