We have investigated whether or not Epstein-Barr virus-transformed lymphoblastoid B cell lines (EBV-BLCL) are able to present Mycobacterium leprae (M. leprae) to antigen-reactive T cell lines and clones. Such EBV-BLCL would provide us with a homogeneous and unlimited source of antigen-presenting cells. Antigen-triggered proliferation of T cells has been studied with co-cultures either with autologous or allogeneic irradiated EBV-BLCL. Our results show that EBV-BLCL are able to present M. leprae as efficiently as peripheral blood mononuclear cells, and that they also function in an HLA-DR-restricted fashion. Apart from their possible in vivo relevance, these results have important practical implications, in particular for the generation and study of M. leprae-reactive T-cell clones.