This study examined the effect of 2-acetyl-2-decarboxy-15(S)-15 methyl PGF2 alpha (PGF2 alpha) on ethanol (EtOH) induced injury in the rat stomach to determine if a PG analogue devoid of antisecretory properties could confer full or partial gastric mucosal protection. Rats were orally administered saline or PGF2 alpha in a dose of 0.5 or 5.0 mg/Kg. Thirty minutes later animals received varying concentrations (i.e. 25%, 50%, and 100%) of EtOH orally. Five minutes following EtOH exposure, they were killed and samples taken from identical regions of the glandular mucosa for microscopic evaluation. All concentrations of EtOH tested damaged the gastric epithelium. The injury induced by 25% EtOH was almost exclusively confined to the surface epithelium and was not altered by either dose of PGF2 alpha pretreatment. In contrast, both 50% and 100% EtOH elicited comparable damage to the gastric mucosa involving both the deep and superficial mucosa of virtually the entire epithelium. The deep injury induced by these two EtOH concentrations was prevented by both the low and high dose of PGF2 alpha. Of particular importance the 5.0 mg dose of PGF2 alpha provided complete protection (i.e. both superficial and deep) to as much as 50% of the mucosa exposed to 50% or 100% ethanol. These findings indicate that PGF2 alpha possesses "cytoprotective" properties involving both the superficial and deep epithelium that are dose related.