Although the primary structure and catalytic cycle of the sarcoplasmic reticulum Ca2+‐ATPase has been revealed, it is not well understood whether functional Ca2+ pump proteins exist in a monomeric or an otigomeric state in native skeletal muscle membranes. Here, we show that the Ca2+‐ATPase tends to form high molecular weight complexes, estimated to be dimers and tetramers using immunoblotting of two‐dimensionally separated microsomal membranes following crosslinking. This agrees with both electron microscopical and biochemical findings which demonstrate that Ca2+‐ATPase clusters are the predominant molecular species in native membranes and that oligomerization may play a role in cooperative kinetics and enzyme stabilization.