The expression of Ia antigen in rat keratinocytes and gut epithelium was found to be inducible by a variety of immunological stimuli. Graft-vs.-host disease (GvHD) was accompanied by the appearance of Ia antigen in both sites, whereas local immunological stimuli, such as a contact-sensitizing agent applied to the skin and Trichinella spiralis infection of the gut, caused the expression of Ia antigen confined to the sites of contact of these stimuli with the tissues involved. Both T helper and T cytotoxic/suppressor subsets of parental lymphocytes, used to produce GvHD in F1 hybrid recipients, induce Ia expression in the skin and gut of these hosts, but simultaneous removal of both subsets from the donor inocula prevented induction. The Ia antigen expression associated with GvHD was shown to be of host origin but was not acquired from bone marrow-derived cells. Attempts to detect Ia antigen in serum or lymph of rats with GvHD gave negative results, and it was shown that Ia+ cells in the lamina propria of the small intestine did not take up detectable amounts of Ia antigen from the Ia+ intestinal epithelium. It appears that the local recognition of antigen by T lymphocytes can result in the induction of Ia antigen in keratinocytes and in the epithelial cells of the intestine. This antigen is synthesized by the cells in which it is found, and the observation that immunological stimuli are responsible for its appearance suggests that its role is an immunological one. Failure to find evidence that the gut epithelium Ia antigen was transferred to lymph or taken up by other Ia+ cells in the intestinal villi supports the view that this Ia (and, by analogy, that found in keratinocytes) serves a local function, and the possibility that it is involved in antigen presentation to T cells is discussed.