Resistance to experimental autoimmune encephalomyelitis (EAE) induced by vaccination with a peptide representing amino acids 39-59 of the rat T cell receptor (TCR) V beta 8 element has been ascribed to the induction of protective antibodies and T lymphocytes, both recognizing the V beta 8 TCR peptide (TCRP) as well as V beta 8 TCR-expressing encephalitogenic lymphocytes. In this study immunization with the V beta 8 TCR peptide conferred partial resistance to active induction of EAE in three of six rats. The immunoregulatory role of TCRP-specific T cells in resistance to EAE was investigated. In vitro, CD4+ T cell lines reactive with the V beta 8 TCRP did not respond to encephalitogenic V beta 8 TCR-bearing cell lines nor did they impair their MBP-induced activation. In vivo, activated TCRP-specific line cells did not ameliorate actively induced EAE. The beneficial effect of V beta 8 TCRP-vaccination on the course of EAE may be due to the induction of protective antibodies. Neither before, nor during or after EAE did we observe a cellular response to the V beta 8 TCRP in lymph nodes or spleens of MBP-immunized animals. Moreover, we were not able to establish TCRP-specific T cell lines from EAE rats, but from all rats immunized with the TCRP. Our data do not support the assumption that V beta 8 TCRP-reactive CD4+ T cells are the population operative in resistance to EAE after recovery from disease.