The 4-1BB antigen has been recently demonstrated to be a 30 kDa inducible T-cell antigen and is expressed on the cell surface of activated splenic T cells and thymocytes. This novel T-cell antigen also associates physically with the T cell-specific protein tyrosine kinase, p56lck. We show here that the inducible T-cell antigen 4-1BB is expressed on activated intestinal intra-epithelial T lymphocytes (IEL). After activation, or in the presence of IL-2, the activated IELs showed higher levels of 4-1BB. Functional studies revealed that the activated IELs triggered with anti-4-1BB monoclonal antibody could enhance the level of IEL cytotoxicity against anti-CD3-secreting hybridoma cells. Cross-linking of anti-4-1BB antibody also enhanced the proliferation of IELs. These results suggest that the inducible antigen 4-1BB has broad biological functions which not only play a role in activated splenic T cells and thymocytes but also in the mucosal immune system.