The corneal endothelium from six humans (three contact lens wearers and three non-contact lens wearers) was examined. Scanning electron microscopy confirmed endothelial polymegethism. Observations with the transmission electron microscope showed that an oblique reorientation of the lateral walls of the endothelial cells had occurred in the contact-lens-wearing group of corneas. The endothelium of the contact lens wearers also showed some inter- and intracellular edema but were otherwise of a healthy appearance containing normal organelles. The oblique reorientation of the lateral wall of the endothelial cell allows for the possibility that a cell with a large anterior surface area may have a small posterior surface area or vice versa. Thus, polymegethous cells may not vary in cell volume. This hypothetical alternative to current theories of contact lens-induced polymegethism should be explored in future research.