While sensitization of Lewis rats with BP/IFA does not induce EAE, recipients given BP/IFA-sensitized cells after culture with BP do develop EAE. To clarify the pathophysiology responsible for this discrepancy, cell dynamics were studied in the recipients. The CD4+ T cells from BP/IFA-sensitized donors showed no proliferative response to BP and no change in cell size or surface molecule expression, even in the presence of BP in culture. On the other hand, the recipient cells proliferated vigorously, regardless of the presence or absence of BP. In this case, a large number of CD4+ blastoid T cells was generated only in the presence of BP in culture. Such cells showed marked upregulation of CD4, CD2, class I and II MHC, and IL2 receptor molecules, a finding we also observed in the case of BP-cultured cells from BP/CFA-sensitized rats with severe EAE. The proportion of CD4+ blastoid T cells generated after culture depended on the number of cells transferred and on the presence of BP in culture, and closely correlated with the severity of EAE in the recipients. These data suggest that BP/IFA-sensitization can also induce BP-reactive cells capable of becoming CD4+ blastoid T cells with marked upregulation of CD4, CD2, class I and II MHC, and IL2 receptor molecules directly related to potent encephalitogenicity, in vivo.