The mechanisms responsible for gut repair after burn injury have not been established. Polyamines are required for eukaryotic cell growth and differentiation. The enzyme ornithine decarboxylase (ODC) catalyzes the rate-limiting step in polyamine biosynthesis. The role of ODC activity in repair of injured small bowel mucosa after burns has not been investigated. This study examined the effects of burn injury on gut mucosal mass and regulation of ODC gene expression and ODC activity in small bowel mucosa. After an overnight fast, 18 male Sprague-Dawley rats (250 to 300 g) were randomized into sham, 20% burn, or 60% burn groups. We measured ODC activity, mucosal weight, deoxyribonucleic acid (DNA) content, and protein content in proximal and distal small bowel mucosa at postburn intervals of 0, 3, 12, 24, and 48 hours. Gut mucosal ODC messenger ribonucleic acid (mRNA) levels were determined. Burn injury caused significant atrophy of the gut mucosa by 12 hours postburn; restoration was evident by 48 hours after burn. ODC activity was increased in the proximal small bowel at 12 and 24 hours after burn in the rats in both the 20% burn and 60% burn groups; by contrast, only rats in the 60% burn group had increased ODC activity in the distal small bowel. ODC mRNA levels increased in the proximal gut mucosa as early as 3 hours after the burn and returned to control values after 24 hours. These data show that mucosal restoration begins soon after burn injury and that the induction of ODC mRNA and ODC activity are important events.