We have studied the antigen specificity and processing requirements of three vaccine-induced cloned human T cell lines specific for HBsAg, the envelope protein of hepatitis B virus. Each T cell line recognized endogenously expressed antigen as well as exogenous antigen. Two clones required endosomal processing, both for exogenous and endogenous antigen; while the other T cell line depended on nonendosomal processing to generate antigenic peptides from both endogenous and exogenous antigen. Thus, the two processing pathways are accessible to exogenous and endogenous antigen. These results suggest that vaccine-induced T cells can participate actively in the immune response to live virus.