The purpose of the present study was to determine in the rat whether parenteral aspirin, like topical aspirin, injures the gastric mucosa by diffusely disrupting the gastric mucosal barrier to hydrogen ion back-diffusion. Back-diffusion studies, including ion fluxes and lumenal potential difference, were performed in control situations and either 0.5 or 4 h after the intraperitoneal administration of sodium acetylsalicylate. Gastric mucosal lesions were scored. After 0.5 h, lesions developed but the barrier was intact. However, after 4 h, lesion formation was more severe and changes characteristic of diffuse barrier disruption, fall in potential difference and increased loss of hydrogen ion occurred. Since lesions occurred before evidence of diffuse barrier disruption could be detected, we conclude that in the present model diffuse barrier disruption is a consequence rather than a cause of lesions.