A distinctive form of gastritis, characterized by lymphocytic infiltration of pit epithelium, has recently been described in association with evidence of Campylobacter pylori infection. We have evaluated simultaneous small bowel and gastric biopsies from 22 patients with diarrhea or malabsorption, all of which showed small bowel changes characteristic of sprue or spruelike disease. In 10 of 22 patients, striking lymphocytic gastritis was identified. Cases positive for lymphocytic gastritis had a mean of 46.5 lymphocytes per 100 epithelial cells, compared with a mean of 3.5 in normal gastric controls and 5.1 in abnormal controls, including cases with Campylobacter gastritis. Concurrent small bowel biopsies had a mean of 47.2 lymphocytes per 100 epithelial cells. Cases without lymphocytic gastritis had means of 10.8 and 39.9 lymphocytes per 100 gastric and intestinal epithelial cells, respectively. Campylobacter organisms were identified in only 1 of the 10 patients with lymphocytic gastritis and in 3 of the 12 patients without lymphocytic gastritis. Intraepithelial lymphocytes in small bowel and stomach were positive for the antibody MT-1, indicating a T-cell infiltrate at both sites. These findings suggest that lymphocytic gastritis may occur as a manifestation of celiac sprue or spruelike disease and that the lymphocytic infiltration of celiac sprue may affect gastric epithelial mucous cells.