HLA class II molecules may be induced on non-lymphoid cells by gamma-interferon (IFN-gamma). We investigated if HLA class II molecules induced by IFN-gamma on the HT29 colonic carcinoma cell line are functional, i.e. if they may be recognized by allogeneic T cells. We found that IFN-gamma-treated HT29 (HT29IFN) cells could not induce primary proliferative responses of peripheral blood T lymphocytes, nor were they able to induce proliferation in T-lymphocyte clones (TLC) specific for HLA class II molecules found on HT29IFN. However, in the presence of exogenous interleukin 2 (IL-2), 1 of 5 DQw8-specific TLC proliferated when restimulated with HT29IFN, and 3 of these 5 TLC could very effectively inhibit the growth of HT29IFN, probably due to a cytotoxic effect. Both the proliferative response and the cytotoxicity were inhibited by anti-DQ MoAb. We conclude that T cells may recognize HLA-DQ molecules on non-lymphoid cells, which may be of relevance for autoimmune diseases, graft-versus-host disease, and possibly for the recognition of malignant cells.