BACKGROUND The search for the ideal dural substitute continues, inasmuch as available materials have significant limitations. Xenogeneic porcine small intestinal submucosa (SIS) has been successfully used as a soft tissue graft in several body organ systems, and it was logical to evaluate its use as a dural replacement. METHODS Twenty rats underwent bihemispheric craniectomy with dural resection. SIS onlay grafting on one side was performed. Histologic assessment was obtained at 7 and 28 days after dural grafting and included descriptive evaluation and quantitative scoring of graft-site thickness, vascularity, and cellular density. The total scores for the respective groups were compared using the Student's t test, significance being accepted for a p value < 0.05. RESULTS Histologic evaluation showed graft infiltration by spindle-shaped mononuclear cells, deposition of connective tissue, and neovascularity. This pattern is consistent with the previously described incorporation and remodeling of the SIS graft at other sites. A significant difference between the histologic scores of the SIS graft site and control site was found at 7 days (3.4 +/- 0.8 versus 0.1 +/- 0.1) and at 28 days (4.6 +/- 1.1 versus 2.2 +/- 0.5). No evidence of adverse effect on the underlying cortex was observed. CONCLUSIONS The results of this preliminary study utilizing porcine SIS as a dural substitute are promising and therefore justify further chronic studies.