Early ultrastructural changes of surface epithelial cells isolated from rat gastric mucosa caused by 15% ethanol were studied. The effect of 16,16-dimethylprostaglandin E2 (16,16-dimethyl-PGE2) on these changes was also examined. Findings by transmission electron microscopy showed ballooning and decreased density of mitochondria in addition to loss of microvilli and partial disruption of the surface cell membrane in cells exposed to 15% ethanol, although the nucleus looked normal. These ultrastructures were well preserved even after exposure to 15% ethanol when the cells were treated with 10(-6) M 16,16-dimethyl-PGE2 beforehand. These results may indicate that the surface cell membrane and mitochondria are the major targets for early injury by ethanol and protection by 16,16-dimethyl-PGE2 in surface epithelial cells. The mechanism by which 16,16-dimethyl-PGE2 prevents the damage is not known.