The elucidation of the molecular architecture of cell membranes is a central goal for cell biology, as structure lies at the heart of function. The erythrocyte plasma membrane has long provided a favored testing ground for this inquiry. Human red blood cells are readily available, relatively homogeneous, and relevant to medicine. Their plasma membranes can be easily isolated intact and essentially free of contamination from other cells, organelles, and cytoplasmic contents. This membrane is complex enough to be interesting and, to some degree, representative, yet it is simple enough to be analyzed as a whole. These circumstances make it likely that the human red cell plasma membrane will be the first whose molecular anatomy is known in any degree of satisfying detail. The literature concerning the proteins of erythrocyte membranes and membranes in general has been the subject of repeated review (1 9). This article will focus on the localization and modes of association of individual major polypeptides within the human red cell membrane.