A clinicopathologic and immunohistochemical review was made of 24 cases of distinctive nerve sheath tumors located in the gastrointestinal tract. The tumors were microscopically evident in the presence of peripheral lymphoid cuffing and benign nuclear atypia. The tumors arose in the muscularis propria of the stomach in 23 cases and in the ascending colon in 1 case. The patients included 9 men and 15 women whose ages ranged from 36 to 78 years (average, 58). No recurrence has developed in any patient who underwent resection. Although positive immunostaining for S-100 protein, Leu 7 antigen, and laminin might support the schwannian nature of these tumors, the positive immunoreactivity for glial fibrillary acidic protein (GFAP) indicated the possibility of a myenteric plexus origin. The pattern of S-100 protein immunostaining differed from that seen in cases of gastrointestinal stromal tumors associated with von Recklinghausen's neurofibromatosis or that noted in cases of conventional leiomyomas. We propose that these tumors be designated as benign schwannoma of the gastrointestinal tract.