Acetaminophen protects gastric mucosa in vivo against acute drug-induced damage and has also been shown to protect gastric epithelial cells in vitro. Protection afforded by acetaminophen in vitro is not associated with increased prostaglandin output. The present study evaluated whether protection of gastric epithelial cells by acetaminophen in vitro may be mediated by endogenous sulphydryls. Monolayers from a well-differentiated human gastric epithelial cell line were studied. Sodium taurocholate was used as a damaging agent and cell damage was assessed by the 51Cr release assay. Acetaminophen dose-dependently protected gastric cell monolayers against damage induced by sodium taurocholate. The sulphydryl blocker iodoacetamide dose-dependently decreased the concentration of nonprotein glutathione and cysteine and counteracted the protection afforded by acetaminophen. This suggests that sulphydryl compounds may mediate the protection of gastric epithelial cells by acetaminophen in vitro.