We recently found that stress increases gastric and duodenal ornithine decarboxylase (ODC) activity and damages both tissues. The current study investigated whether corticosterone induces ODC activity in gastric and duodenal mucosa in rats and compared plasma corticosterone levels after stress and treatment with corticosterone to determine whether this hormone mediated the effects of stress on the mucosa. Rats were fasted 22 h, placed in a restraint cage, and immersed in water to the xiphoid process for 6 h. Stress markedly increased plasma corticosterone levels; the increase was 10.5 times control and lasted the duration of stress. The maximum increase was observed 1 h after a single injection of corticosterone (5 mg/kg sc) and represented 11.1 times control values. By 6 h, plasma corticosterone had returned to normal levels. A single injection of corticosterone had no effect on the gastric mucosa, but duodenal ODC was increased significantly from 4 to 8 h after injection, peaking at 6 h. Histological examination revealed no damage in either tissue. Administration of corticosterone three times daily for 3 days dramatically elevated ODC activity and produced significant microscopic damage. The surface epithelium of the stomach was disrupted, with many surface cells shed, and most villi were absent from the duodenal mucosa. Corticosterone also markedly decreased DNA and RNA content of both tissues. Inhibition of ODC with DL-alpha-difluoromethylornithine additionally decreased DNA, RNA, and protein content, exacerbating the damage.(ABSTRACT TRUNCATED AT 250 WORDS)