The effects of activity wheel stress on brain regional norepinephrine (NE) and 3-methoxy-4-hydroxyphenylglycol (MHPG) content and on the occurrence of gastric lesions were investigated. Multiple gastric lesions were present in the stomachs of all rats exposed to activity wheel stress (AW). No gastric lesions were observed in any of the food consumption (FC) or untreated (UC) control rats. In AW rats, NE levels were significantly different (p < 0.05) from UC and/or FC rats in the hypothalamus (––25%), striatum (+120%), and hippocampus (––25%). MHPG levels in AW rats were significantly (p < 0.05) elevated in the hypothalamus (130%), thalamus (95%), neocortex (80%), midbrain (160%), pons medulla (30%), and cerebellum (100%), indicating increased NE turnover in these brain regions. The data are discussed in terms of a possible role for brain NE in the mediation of activity stress-induced gastric lesions.