In experimental allergic encephalomyelitis (EAE) myelin basic protein (MBP) specific T cells differ in their encephalitogenic potential. To investigate the functional diversity of human MBP specific T cell lines, we analysed their cytotoxic activity against human astrocytes and monocytes. Five out of 14 MBP specific T cell lines killed astrocytes in the presence of MBP. Nevertheless, all lines lysed blood derived monocytes. T cell lines that lysed astrocytes efficiently in the presence of MBP, recognized peptide aa 80–99/86–105 in context with HLA-DRB5*0101, peptide aa 50–69/61–83 in context with HLA-DRB1*1501 and peptides aa 139–153, and aa 148–162 in context with HLA-DRB1*0101. There was no correlation of MBP-mediated lysis of astrocytes with TCR-V β usage, HLA-restriction and the production of tumor-necrosis-factor- α (TNF- α), lymphotoxin (LT) and interferon- γ (IFN- γ). Different lysis of astrocytes, however, revealed a functional heterogeneity of MBP specific T cells, which was not observed by using monocytes as targets.