Recently there has been evidence suggesting that gamma delta receptor-bearing T cells may play a role in both multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE). We have recently described approaches for the generation of encephalitogenic T-cell populations from EAE-resistant strains of mice. Using encephalitogenic T-cell lines and clones generated from wild-type C57BL/6 mice we have studied adoptively transferred EAE in C57BL/6-TCR delta-knockout mice. We now report that the adoptive transfer of encephalitogenic T cells into TCR delta T-knockout mice leads to clinical EAE that is not significantly different in severity or time course than that seen after transfer into wild-type C57BL/6 mice. We conclude that gamma delta T cells do not play an integral role in the mediation or regulation of the effector-phase mechanisms in EAE. (C) 1998 Academic Press Limited.