Abstract Sarcoplasmic reticulum Ca 2+-ATPase was digested with proteinase K, V8 protease and trypsin in the absence of Ca 2+. Unphosphorylated enzyme was rapidly degraded. In contrast, ADP-insensitive phosphoenzyme formed with P i and phosphorylated state analogues produced by the binding of F − or orthovanadate, were almost completely resistant to the proteolysis except for tryptic cleavage at the T1 site (Arg 505). The results indicate that the phosphoenzyme and its analogues have a very compact form in the cytoplasmic region, being consistent with large domain motions (gathering of three cytoplasmic domains). Results further show that the structure of the enzyme with bound decavanadate is very similar to ADP-insensitive phosphoenzyme. Thapsigargin did not affect the changes in digestion time course induced by the formation of the phosphorylated state analogues.