Wound dressings are used as a temporary wound covering to promote wound healing, control wound exudate, and decrease wound contamination as well as evaporative water loss. A new material, porcine small intestinal submucosa, has been used successfully as an arterial and venous graft in both canine and primate animal models with graft patency and infection rates equal to autologous vein. Based on these studies, small intestinal submucosa was used as a biological wound dressing in 20 x 20 mm full-thickness wounds made on Sprague-Dawley rats. In the controls (group I, n = 12), an acrylic frame (20 x 20 mm) was sutured to the wound edges, followed by placement of a thin polyurethane film. In the small intestinal submucosa-treated animals (group II, n = 12), the wound was covered with small intestinal submucosa and then with the acrylic frame and polyurethane film. The wounds were examined both visually and histologically at postapplication days 3, 7, 14, 28, 42, and 56. In addition, the wound contraction rate of 6 animals in both groups was recorded at postapplication day 0 and then at 1 week, 1 month, 2 months, and 3 months. Histological analysis (hematoxylin-eosin and periodic acid-Schiff stains) of the small intestinal submucosa-treated wounds revealed no host-versus-graft rejection and a rate of epithelialization equal to that of the control group. The wound contraction rate was statistically significant (higher; p < .05) in the control group compared to the small intestinal submucosa-treated group. Porcine small intestinal submucosa merits further study as both a biological wound dressing and as a substrate for cultured cells.