Although appendicitis is the most common condition requiring emergency surgery, the pathogenesis of this disease is poorly understood. In this study, local immune responses in acute appendicitis were investigated, using an experimental rabbit model, as well as in different grades of appendicitis in humans. Polymorphonuclear leukocyte (PMN) and plasma cell isotypes infiltration was measured in 24 New Zealand-bred white rabbits following experimental obstruction of the appendiceal lumen for periods ranging from 30 minutes to 24 hours. Significant infiltration of PMNs, IgM, and IgG plasma cells was noted at 30 minutes following obstruction, and IgA plasma cells were noted at 2 hours after obstruction. The immunopathological features observed in the study of human appendicitis clearly demonstrated the role of plasma cell infiltration in the immunopathogenesis of appendicitis. IgA and IgG plasma cells were significantly increased in the lamina propria of both focal and acute suppurative appendicitis, compared with controls (P less than .001). In focal appendicitis, in which the focus of inflammation is confined to only a few serial sections, the increased IgA and IgG plasma cell infiltration was present throughout the entire length of the resected organ. The possibility, as seen in this study, that antigen stimulation of the effector immune system could give rise to appendicitis, provides new insights into the diversity of inflammatory responses contributing to diseases of the intestinal tract. This previously unrecognised concept in the pathogenesis of appendicitis requires further elucidation of the stimulating agent, and in particular the T-cell recognition process.