The effects of zinc deficiency on ethanol-induced ulcers were studied. Rats fed with zinc-deficient diets for 5 weeks showed markedly lowered serum zinc levels and body weights. Ethanol 30% given orally produced gastric mucosal lesions and reduced the glutathione content in the gastric glandular mucosa in their pair-fed non-zinc-deficient controls. Zinc deficiency potentiated the glutathione-depleting and ulcer-producing effects of ethanol. N-acetylcysteine, a sulfhydryl-containing agent, protected non-zinc-deficient rats from lesions produced by 50% ethanol, whereas N-ethylmaleimide, a sulfhydryl-blocking agent, worsened ulceration. It appears that zinc deficiency intensifies ethanol-induced ulceration by permitting greater depletion of the glutathione content in the stomach.