Subpopulations of lymphoid cells were compared with respect to their ability to migrate into the central nervous system (CNS) of mice with acute experimental allergic encephalomyelitis (EAE). In mice with established lesions, the majority of cells homing to the CNS are not presensitized to CNS antigens. B cells had a much reduced capacity to migrate into the CNS of sick mice compared with T cells. However, T cells of both the Lyt-2+ and Lyt-2- subsets homed equally well to the CNS. The relative paucity of B cells in the lesions of EAE and multiple sclerosis may thus partly result from the limited ability of these cells to migrate into the CNS across the blood-brain endothelial barrier. The predominance of Lyt-2- T cells over Lyt-2+ cells in these CNS lesions is unlikely to result from such a difference in homing capacity, but may reflect the ratio of these two cell types in the blood or preferential in situ expansion of the Lyt-2- population.