Reconstitution of cardiac and skeletal sarcoplasmic reticula (SR) $Ca^{2+}-ATPases$ into liposomes requires different conditions for optimum enzymatic activity. In the presence of phosphatidylcholine (PC), maximum activity was obtained at a cholate/$Ca^{2+}-ATPases$/PC ratio (w/w) of 2/1/80 for cardiac SR $Ca^{2+}-ATPases$, and 4.5/1/40 for skeletal SR $Ca^{2+}-ATPases$. Reconstitution of cardiac $Ca^{2+}-ATPases$ did not require the presence of oxalate in the reconstitution buffers, while this was essential for skeletal $Ca^{2+}-ATPases$. The maximum rates of $Ca^{2+}$ uptake by reconstituted vesicles were 700 nmol/mg/min for cardiac $Ca^{2+}-ATPases$, and 960 nmol/mg/min for skeletal $Ca^{2+}-ATPases$. These findings suggest that $Ca^{2+}-ATPases$ from cardiac and skeletal SR require different conditions for reconstitution, even though they have similar amino acid sequences (80% homology) and phospholipid compositions.