We investigated immunostained macrophages in the noninflamed mucosa of Crohn's disease patients. Biopsied specimens from endoscopically normal gastroduodenal mucosa of Crohn's disease, ulcerative colitis, and healthy control patients were studied. Sections were examined immunohistochemically using a monoclonal antibody specific for tissue macrophages (CD68). Immunostained mucosal macrophages in the second part of the duodenum, duodenal bulb, gastric antrum, and gastric body of the Crohn's disease group were more numerous than in the ulcerative colitis and control groups. The characteristic findings of Crohn's disease were aggregations, focal subepithelial dense accumulations, and infiltration throughout the mucosa of macrophages not accompanied by a lymphoid infiltrate. The number of macrophages in the gastroduodenal mucosa bore no relationship with the duration of symptoms, clinical activity, or affected site in the intestine. This suggests that the increased number of macrophages in noninflamed mucosa is a histological change characteristic for Crohn's disease that indicates a persistent latent abnormality involving the entire gastrointestinal tract.