Confluent, cultured, rabbit corneal endothelial cells maintain a polygonal shape which is characteristic of these cells in vivo. When cultured in the presence of EGF (10 ng/ml) and/or indomethacin (1.0 microM), the endothelial cells have markedly different shapes at confluency. By morphometry, untreated cells are polygonal and have a maximum axis of 33 mu; EGF treatment causes a spindle-shaped elongation to 48 mu and indomethacin treatment causes a stellate-shaped elongation to 48 mu. There is a slight increase in cell density. When cells are cultured in the presence of both drugs, elongation is more pronounced to a fibroblastic appearing cell population, with maximum axes of 60 mu and more, but no additive increase in cell density. Continuity of cell borders is often lost. Corneal endothelial cells cultured in the presence of EGF, indomethacin, and PGE2 (0.5 microgram/ml) maintain their polygonal shape; PGF2 alpha is not effective at reversing the drugs' effects. Untreated and EGF-treated cells synthesize and release substantial quantities of PGE2 (2-4 ng/10(4) cells). Indomethacin completely inhibits PGE2 synthesis. It is concluded that PGE2 maintains the polygonal cell shape of the corneal endothelium in vitro and, perhaps, in vivo. The elongated forms of the cell may be related to migration and important in wound closure.