We have recently established chronic relapsing experimental autoimmune encephalomyelitis (CR‐EAE) in SJL mice with a modified protocol. In this model, splenectomy aborts the relapsing–remitting course of the disease, and adoptive transfer of lymphocytes of the local draining lymph nodes (LNs) to naive recipients exacerbates the disease. Adoptive transfer of splenic cells converted acute EAE into CR‐EAE in the naive recipients. In light of the different roles of the spleen and LNs in the evolution of CR‐EAE, we examined by semiquantitative reverse‐transcription polymerase chain reaction (RT‐PCR) whether a differential mRNA expression profile of cytokines and cellular adhesion molecules (CAMs) in spleen versus LN was associated with relapse or remission in CR‐EAE. All the cytokines tested (interleukin‐1β (IL‐1β), IL‐2, IL‐4, IL‐7, IL‐10, interferon‐γ (IFN‐γ)) as well as CAMs (ICAM‐1, ICAM‐2, VCAM‐1, LFA‐1 and CD44) were expressed at substantial levels in both spleen and LNs. Interestingly, disease remission was found to be associated with an increased mRNA expression of IL‐2 and IFN‐γ in LNs and a decreased IL‐10 mRNA level in the spleen. On the other hand, an increased mRNA expression of VCAM‐1, LFA‐1 and CD44 was observed in the spleens in comparison with that in LNs of mice, with remission. During relapses, mRNA expression of the tested molecules did not significantly differ between spleens and LNs. Our results suggest that a differential and polarized expression profile of certain cytokines and CAMs in spleen versus LN could provide molecular correlates of the cyclic pathogenesis of CR‐EAE.