Intracellular free calcium is regulated by Ca++-ATPase, one form present on the plasma membrane (PM Ca++-ATPase) and the other on sarcoplasmic (endoplasmic) reticulum (SR/ER Ca++-ATPase). An endogenous inhibitor of SR Ca++-ATPase from human placenta was shown to be present in normal placenta and the activity was not detectable in placenta from preeclamptic patients. The inhibitor was distributed in cytosol and microsomes. The inhibition of Ca++-ATPase by this inhibitor was concentration-and time-dependent. The inhibitor neither bound to DEAE-nor CM-sepharose resins at pH 7.5 and 8.5. Furthermore, it was heat stable for 15min up to 55°C and completely destroyed at 80°C in a few minutes. It was also observed to be stable at room temperature for at least 3 months. The purification and characterization of this inhibitor would be valuable in achieving an understanding of the normal regulation of Ca++-ATPase in the placenta during pregnancy.