The diffusion measurements of glycoproteins have further supported a fluid mosaic model of membrane structure, but the basis of the lower apparent diffusion coefficients in biological membranes remains incompletely understood. In the specific case of glycoproteins with a single alpha-helix spanning the membrane, studies indicate that the major frictional drag is in the external protein layer and not the bilayer. Only in the erythrocyte membrane does the internal protein layer clearly control the lateral diffusion coefficient of a glycoprotein with a large cytoplasmic domain. In cultured cells, the barriers to lateral displacements over long distances are primarily on the cytoplasmic surface and not in the external matrix. Active movements of individual or small groups of glycoproteins both forward and rearward on cells appear to result from the interactions with moving cytoskeletal structures. Membrane turnover as well as transient attachment to the cytoskeleton can produce dynamic domains in the membrane that would depend on motile activity. Recent technological advances enable simultaneous monitoring of specific cell functions and glycoprotein motility, making it possible to correlate membrane fluidity and active glycoprotein movements with cell function.