A large number of the endothelial cells remain attached to the overlying cornea throughout life. The mechanism for this adhesion has not been studied in the past. The lack of anatomical modifications known to be concerned with the cell adhesion suggested the possibility of physiological forces being involved in securing cellular adhesion to the overlying corneal tissue. 81 pig eyes were used to study the effects of the various physiological processes on the endothelial adhesion. The influence of osmotic pressure (27 eyes; range: 75-1708mOsm), cell metabolism (18 eyes; 4 degC vs 34 degC storage), inhibition of Na+-K+ pumps (18 eyes; 10-4M Ouabain), and deprivation of Ca+2 (18 eyes; 2.5/5.0 mM EDTA) on the endothelial adhesion were evaluated by testing the adhesion with jeweler's forceps and scraping. None of these experiments resulted in a reduced endothelial adhesion or allowed the removal of sheets of the endothelial cells suggesting that the cell adhesion is not influenced or controlled by a physiological mechanism. These results lead to the conclusion that a morphological arrangement for the anchoring of the endothelial cell to the posterior limiting lamina is the most likely answer to the perplexing phenomenon of this strong and lasting attachment.