We previously reported that acute experimental autoimmune encephalomyelitis (EAE), induced by active immunization of SJL mice, could be converted into chronic relapsing EAE (CR‐EAE) by a pretreatment with neuroantigen and killed mycobacteria 2 months earlier. This finding indicates that immune memory, established by the pretreatment, influences the subsequent EAE induction. The present study shows that splenectomy and lymphadenectomy, applied 1 week before the subsequent active immunization of the pretreated mice, efficiently abort the chronic nature of CR‐EAE. Furthermore, we have found that adoptive transfer of lymphocytes from the spleen (but not of those from the local draining lymph nodes) of the pretreated mice to naive syngeneic recipients 1 week before the acute EAE‐induction immunization results in the development of CR‐EAE. On the other hand, the transfer of lymphocytes from the local draining lymph nodes aggravates the acute disease. These data support a critical role for immune memory of the previous suboptimal challenge in the development of chronic relapsing demyelinating disease.