Both gastric ulceration and activation of the hypothalamo-pituitary adrenal axis are considered integral to the stress response, and a causal relationship between the two has been suggested. In the present study, corticosterone secretion in rats was either stimulated with CRF or lowered with metyrapone during a known ulcerogenic stress. Reduction of circulating corticosterone during the stress had no effect on ulceration severity compared to saline-treated stressed control rats. Treatment with CRF in stressed animals reduced ulceration severity. The mechanism of this protective effect remains unclear. The findings do not support a simple causal relationship between adrenocortical activity and gastric ulceration.