A new in vitro model for ethanol-induced gastric damage is described. The stomach was dissected from the rat, a polyethylene cannula introduced into the remnants of the esophagus, and the pyloric end tied off. With the cardiac and pyloric regions of the stomach secured by thread to a vertical glass rod or tube, the whole was suspended in an organ bath containing aerated Krebs solution. Fifteen minutes later, ethanol was introduced via the esophageal cannula. After an additional 60 min, the stomach was removed from the Krebs solution, opened along the mid line, and the lesions studied. Comparisons were made with a conventional in vivo model. Results show that the lesion number, length, and total lesion area obtained by the in vitro model were comparable to those obtained in the older in vivo model. Histopathologically, lesions induced by both models were also comparable. Clonazepam, a drug previously used in the in vivo model, was tested in this model. Results indicate that clonazpam protected against ethanol-induced gastric damage in vitro. The new model provides a method to study the action of drugs on the stomach alone and to exclude in indirect actions of drugs via other sites in the body.