Amphiphilic compounds with distinct apolar and polar parts are readily intercalated into the erythrocyte membrane. When intercalated into the membrane, amphiphiles are probably orientated so that the polar head is at the polar-apolar interface of the lipid bilayer and the hydrophobic part within the apolar core of the bilayer. However, by virtue of their difference in molecular shape from the bulk lipids of the lipid bilayer, it is possible that the intercalated amphiphiles are partly segregated from bulk lipids and accumulate at protein-lipid interfaces in the bilayer, where the packing of the bilayer lipids may be less ordered. Our studies show that amphiphiles, when intercalated into the erythrocyte membrane, trigger alterations in several membrane-connected functions. Some of the alterations induced (decreased osmotic fragility, increased passive potassium fluxes) seem to be due to non-specific interactions of the amphiphiles with the membrane, whereas other functions (ion transport mediated by membrane proteins, regulation of cell shape) seem to be sensitive to particular features of the amphiphiles. Our studies indicate that the intercalation of amphiphiles into the erythrocyte membrane must involve rearrangements within the lipid bilayer. We have suggested that, when intercalated into the lipid bilayer, amphiphiles trigger a rapid formation of non-bilayer phases, which protect the bilayer against a collapse and bring about a trans-bilayer redistribution of intercalated amphiphiles as well as of bilayer lipids. At high sublytic concentrations, this process may also involve a release of microvesicles from the membrane.