Human gastric and colonic mucosa obtained at operation was cut into small pieces and incubated with different concentrations of ethanol. 2. Ethanol (5-40%) caused a concentration-dependent increase in the amounts of prostaglandin E (PGE), thromboxane B2 (TXB2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and (up to 20% ethanol) leukotriene C4/D4 (LTC4/D4) in incubates of mucosal pieces from either region. 3. Higher concentrations of ethanol usually caused small increases or reductions of eicosanoid levels; gastric mucosal PGE and 6-keto-PGF1 alpha were still increased by 100% ethanol, whereas TXB2 was unaltered, and LTC4/D4 was reduced. With the colonic mucosa, 100% ethanol increased PGE but reduced the other eicosanoids. 4. Gastric mucosal pieces incubated in water or phosphate buffer yielded generally similar amounts of eicosanoids. However, colonic mucosa yielded more when incubated in water, possibly indicating a greater sensitivity to osmotic damage. This difference between the two regions is consistent with the ability of the gastric mucosa to resist damage by water on its epithelial surface.