gamma Interferon (IFN-gamma) caused remarkable increases in class I (H-2Kk) and class II (I-Ak) antigens throughout the body by 6-9 d. Heart, kidney, and adrenals showed increases of 4-8 times their previous levels of class I antigen content, while the pancreas and small intestine increased 13-17-fold. Lesser increases were found in spleen, liver, and lung, which showed higher resting antigenic potency. Increases of class II antigenicity of 6-10-fold were found in heart, kidney, pancreas, lung, liver, adrenal, and small intestine, with lesser increases in thymus and spleen, and none in lymph node. Topographical analysis revealed that IFN-gamma induced class I and II antigens on most tissues in a highly selective fashion. For example, the renal proximal tubules expressed large amounts of both class I and II antigens, whereas the distal tubules and collecting ducts did not. In some epithelial cells class I and II determinants were induced only on the basal aspects of the cell membrane. IFN-gamma caused a remarkable increase in class II-positive dendritic cells in the liver, pancreas, salivary glands, and thyroid. Whether these cells were of local or systemic origin is uncertain, but the finding of a simultaneous depletion of dendritic cells from lymph nodes and spleen raises the possibility that they may have been derived, at least in part, from these sites. The dynamic and selective induction of class I and II antigen expression by IFN-gamma is likely to be important in regulation of the immune response in tissues.