Recent results have demonstrated that Ia-like antigen expression in animal tissues is not restricted to cells associated with immune functions. Whether this phenomenon occurs in normal human tissues has been investigated in this study by indirect immunofluorescence on cryostat sections using monoclonal antibodies to framework determinants of Ia-like antigens. The results of this study show that Ia-like antigens are expressed on several normal human tissues of different embryonic origin. These include the epithelium of the gastrointestinal tract, urinary bladder, bronchial glands, thymic reticuloepithelial cells (entodermic origin), epithelium of mammary gland, acinar cells of parotid, astrocytes (ectodermic origin), alveolar macrophages, Kupffer cells, glomerular and peritubular renal endothelium, endometrium, and Langerhans cells (mesodermic origin).