The processing and presentation of whole myelin basic protein (MBP) and a 12 amino acid encephalitogenic peptide were investigated using MBP-immune and peptide-immune murine T cell lines. Myelin basic protein is the major component of central nervous system (CNS) white matter capable of inciting an autoimmune response which leads to the disease, experimental allergic encephalomyelitis (EAE), in a number of animal species. MBP-immune T cell lines caused a form of adoptively transferred EAE when injected into naive, syngeneic recipients. It has been found that both whole MBP and peptide required processing in order to induce proliferation of the T cell lines. The proliferative response was greatest when MBP was processed under conditions in which proteolysis was prevented. The demonstration that activation of encephalitogenic MBP immune T cells requires a processed form of MBP may have relevance to the human inflammatory CNS demyelinating condition, multiple sclerosis, for which EAE is the prime animal model.