AbstractFor many years the red cell membrane has served as an extraordinarily valuable model for membrane structure and function. During the past 2 decades, the biochemical concept of the membrane skeleton was established, and, with the help of electron microscopy, a partial depiction of this structure evolved. Newer biophysical approaches designed to measure distances between various components of membrane skeleton as well as distances between the membrane skeleton and the overlying bilayer should now help to define this structure more realistically. Fluorescence resonance energy transfer, single photon radioluminescence, and total internal reflectance are three biophysical techniques that will enable us to measure such distances over a substantial range, which extends from a few Angstroms to ∼2 μm. The ability to make such measurements in intact cells and in fully hydrated, undenatured membrane preparations should add a new dimension to our understanding of the structure of the red cell membrane. © 1993 Wiley‐Liss