The aim of this study was to investigate whether chronic alcohol abuse alters the number and distribution of mononuclear cells of the duodenal mucosa. The number of common leukocyte antigen (CLA)-positive interepithelial lymphocytes (IEL), B lymphocytes (BL), IgA-producing plasma cells (IgA-PC), and macrophages (MP) was quantitatively evaluated in biopsies of the duodenal mucosa of patients with alcohol abuse compared to subjects without alcohol abuse. Biopsies from the descending part of the duodenum were obtained by endoscopy from two groups of patients with chronic alcohol abuse (group A1, abstinence <5 days, N = 21) and group A2 abstaining 5-10 days (N = 6). Twenty-five subjects without alcohol abuse served as controls (C). Immunohistochemical staining was done by avidin-biotin-complex method. In addition, the content of IgA in the plasma cells was determined by using a TV-densitometric method. The number of B-lymphocytes in the lamina propria was increased by 37% in group A1 (P < 0.005). A distinct decrease was observed in group A1 compared to C in the number of IEL that were CLA positive (-50%, P < 0.025) and in the number of macrophages (-54%, P < 0.025). In group A2 the differences in the number of B lymphocytes and macrophages were no longer seen. In A1, there was no significant change in the number of IgA-producing plasma cells or in the number of interepithelial lymphocytes counted after H&E staining compared to the controls. There was no difference in content of IgA in the IgA-producing plasma cells. From these results it is concluded that chronic alcohol abuse significantly influences the gut-associated immune system, possibly by increasing the permeability of the gut mucosa to macromolecules that act as antigens.