Studies of lipid-protein interactions in double-reconstituted systems involving both integral and peripheral or lipid-anchored proteins are reviewed. Membranes of dimyristoyl phosphatidylglycerol containing either myelin proteolipid protein or cytochrome c oxidase were studied. The partner peripheral proteins bound to these membranes were myelin basic protein or cytochrome c, respectively. In addition, the interactions between the myelin proteolipid protein and avidin that was membrane-anchored by binding to N -biotinyl phosphatidylethanolamine were studied in dimyristoyl phosphatidylcholine membranes. Steric exclusion plays a significant role when sizes of the peripheral protein and transmembrane domain of the integral protein are comparable. Even so, the effects on avidin-linked lipids are different from those induced by myelin basic protein on freely diffusible lipids, both interacting with the myelin proteolipid protein. Both the former and the cytochrome c /cytochrome oxidase couple evidence a propagation of lipid perturbation out from the intramembrane protein interface that could be a basis for formation of microdomains.