A significant fraction of orally consumed ethanol is metabolized by the alcohol dehydrogenase (ADH) enzyme present in the gastric mucosa. Human studies have shown that this "first pass metabolism" of ethanol correlates quite closely with gastric ADH activity which has been demonstrated to be greater in men than women. The present study was undertaken to determine if gender influences the magnitude of ethanol-induced injury in rat gastric mucosa and whether any differences can be linked to altered levels of ADH activity. Since prostaglandins (PGs) have been shown to markedly attenuate the severity of gastric injury induced by ethanol in the rat stomach, a further goal of this study was to determine whether the efficiency of PG's protective action was in any way influenced by gender. Accordingly, both male and female rats were pretreated subcutaneously with 16,16-dimethyl PGE2 (10 micrograms/kg) or saline 30 minutes prior to administering an oral dose of 50% ethanol in saline or saline alone. They were then sacrificed 5 minutes later. In a portion of animals (n = 6 per group), samples of mucosa from the glandular stomach were obtained and kinetic activity of ADH determined. In another portion of animals (n = 6 per group), gastric tissue samples from the glandular mucosa were examined by light microscopy and the magnitude of mucosal injury quantified. Alcohol-treated females showed significantly (p less than 0.05) less superficial and more deep mucosal injury than male counterparts. Further, ADH kinetic activity in female rats was significantly less than that observed in male counterparts of similar weight (83% of males; p less than 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)