We present an immunohistochemical study of accessory cells in acute appendicitis and ulcerative colitis (UC). By comparing these two diseases, it is possible to distinguish between changes associated with inflammatory bowel disease and those resulting from nonspecific intestinal inflammation. Nine total colectomy specimens from patients with UC, in which the appendix was also involved, were compared with nine cases of acute appendicitis. Accessory cells were stained for CD68 (PGMI), ACPI (acid cysteine proteinase inhibitor), S100 protein, MAC387 (calgranulin), CD1a, factor XIIIa, and WR18 (HLA class II). In ulcerative colitis, but not acute appendicitis, there was extension of a network of S100 positive dendritic cells into the crptal mucosa, and these S100-positive dendritic cells were closely aligned with the epithelium. The epithelium in UC, but not in acute appendicitis, showed intense upregulation of HLA class II, and this was particularly marked at the crypt bases. Dendritic, MAC387-positive cells were seen only in UC. In both diseases there were abundant ACPI-positive accessory cells in the cryptal areas, a population normally restricted to the dome areas. Factor XIIIa- and PGM1-positive cells, although abundant in both conditions, had distributions similar to those that we had previously shown in normal controls. No CD1a-positive cells were identified in either UC or acute appendicitis. We hypothesize that S100 identifies a subpopulation of activated macrophages. The concentration of this subpopulation, in close contact with the epithelium, which also shows altered expression of HLA class II antigens, suggests that a component of the immune response is targeting this area in UC. In addition, we also suggest that the identification of MAC387-positive dendritic cells in UC reflects increased macrophage turnover in inflammatory bowel disease.