Increased expression of class II antigens (HLA-DR, human:Ia murine) on epithelial cells (EC) such as keratinocytes and gut EC suggests a role of the epithelium in the inflammatory response. It has been shown that injection of normal mouse serum (NMS) into nude mice caused an induction of Ia antigen by keratinocytes of the nude mice. The aim of the present study was to determine whether such induction could be observed in gut EC and whether it can be inhibited by cyclosporine A (CyA). Forty nude mice were divided into 4 groups of 10 each, designated A-D. Group A was injected with 0.1 ml of NMS; groups B and C were also injected with NMS and treated with oral CyA for 10 days. The dosage in group B was 30 g/ml and in group C 60 g/ml of drinking water. Group D was injected with serum of nude mice and served as a control group. Biopsies of small intestine and colon were obtained from each mouse and analyzed by indirect immunoperoxidase to identify Ia expression. Small intestine and colon EC were induced to express Ia antigen in most of the mice in groups A and B. A striking reduction in Ia expression was noted in group C. The differences between groups A and C concerning Ia expression on small intestine and colon EC were statistically significant. Our results demonstrate that the nude mouse may serve as a model for the study of Ia expression on gut EC, and that CyA can suppress the expression of Ia antigen also in the gut.