The striking reduction or absence of macroscopic necrotic lesions in rat stomachs exposed to necrotizing agents after treatment with prostaglandins has been described as "cytoprotection." However, the morphologic features of this effect have not been published. We have quantitatively evaluated in semithin sections the amount and depth of gastric mucosal damage to rat stomachs exposed to absolute ethanol with and without prostaglandin (16,16-dimethyl PGE2) pretreatment. Our findings are: (a) Control rats given prostaglandin or 5% ethanol (vehicle) had less than 5% of the mucosal surface damaged and the disruption was limited to superficial, luminal cells. (b) All rats receiving absolute ethanol, with or without prostaglandin treatment, had about 78% of their stomach surface damaged. (c) Prostaglandin treatment reduced the depth of damage by about 20% and virtually eliminated necrotic lesions. (d) Necrotic lesions were found to be regions with deep gland damage accompanied by hemorrhage and hyperemia.