Since brainstem lesion involving dorsal (DR) and median raphe (MR) nuclei have been shown to induce gastric ulcers in fasted rats, the present study was carried out to determine the mechanisms mediating this effect of the lesion, inasmuch as there is indirect evidence for a close correlation between stress-induced gastric ulcers and central serotonergic activity. Acute and simultaneous lesion of both DR and MR in 48 h fasted rats induced a significantly high incidence of gastric ulcer at the end of a 48 h period of food deprivation. Acute selective lesion of either nucleus revealed that the MR nucleus is the structure whose inactivation is related to gastric ulceration. Ulcer incidence was also high in chronically lesioned rats fasted for the same period of time. Normally fed lesioned rats and sham-operated controls did not develop ulcers, indicating that ulcers only occurred when fasting and raphe lesion were combined. We conclude that the raphe nuclei may be involved in the etiology of stress-induced gastric ulcers. The possibility of disinhibition of a general stress-related central system by the raphe lesion is discussed as the main mechanism responsible for gastric ulceration.