We have analyzed the effects of interferon-a//S on MHC expression in the murine kidney, and compared these results with the MHC modulating e f fe c ts of inte r fe ron- 7. Natural murine interferon-a//3 was administered to B 1 0 .B R mice (H-2k), i.p., tw ice daily fo r 3 days. Expression of MHC antigens was assessed on day 4 b y immune operoxidase staining w ith b iot inylated monoclonal antibodies to class I (KkDk) and class II (I-A k) antigens. Inte r fe ron-a/0 s ignificantly decreased the number of class II-positive renal cortical dendritic cells from 62 .0 /mm2 to 12.6/mm2 (P < 0.001). A similar but less dramatic decrease was seen in cardiacdendritic cells. Litle or no change in class II expression was obse rved in proximal tubules orglomeruli. Interferon-a /0 induced marked class I staining in the glomerulus, arterial endothelium, and Bowman’ s capsule. Proximal tubule cells also showed increased class I expression, but wereless responsive than glomeruli. Thus, the effects of inte r fe rona/ s contrast with those of in te r fe ron -7, which increases class II expression on p rox im a l tubules, induces re la t iv e ly more class I expression in prox im al tubules than glomerul i, and increases class II—posit ive dendr itic cells. Furthermore, these results suggest that treatment with interferon-a/j9 may have a complex effect on the immune response to a renalal lograft due to its differential effects on class I and class II ce l l surface expression. © 1990 by Williams and Wilkins.