Passive (adoptive) transfer of experimental allergic encephalomyelitis (EAE) with lymph node cells has been used as a method of analysis of mechanisms of disease induction and protection. Pretreatment of cell donors with CNS tissue prior to active challenge yielded lymph node cells which were unable to induce EAE in normal recipients. Similar pretreatment of recipients with CNS before they were given cells from actively sensitized donors rendered them unreactive to an otherwise highly encephalitogenic cell inoculum. Interference with the formation of sensitized cells is thus only one part of and not the whole explanation for the phenomenon of protection. Mycobacteria-induced protection against EAE similarly created an internal environment in the recipients which did not permit passive transfer of EAE. In each case, protection against EAE was accompanied by inhibition of the delayed dermal reaction to the CNS encephalitogen, myelin basic protein (BP). The site of interference with delayed hypersensitivity, which occurs at some point beyond the initial sensitization, was not defined by the present study. The protected state, which in most animals was not accompanied by detectable antibodies to the encephalitogen, could not be transferred passively to other animals with either serum or lymphoid cells from protected animals.