T-cell clones have been isolated from SJL/J mice after immunization with myelin proteolipid protein (PLP). The cloned cells responded strongly to PLP stimulation in vitro as well as to the synthetic PLP-related peptide 139-151. The response to PLP is Ia mediated, since it was inhibited by monoclonal antibodies to the matched I-As haplotype, but not with antibodies to other I-A haplotypes. Phenotypic analysis using immunofluorescence demonstrated the following characteristics of the clones: Thy-1+, CD4+, CD5+ and CD8-. Injection of 10-30 million PLP-activated cells from one clone induced severe experimental allergic encephalomyelitis in five mice, both clinically and histologically. This represents to our knowledge the first report of PLP-specific encephalitogenic cloned T cells. © 1990.