Experimental autoimmune encephalomyelitis (EAE) is a CD4(+) T cell-dependent, organ-specific autoimmune model commonly used to investigate mechanisms involved in the activation of autoreactive T(h)1 cells. Mitogen-activated protein kinases such as c-Jun N-terminal kinase (Jnk) 1 and 2 play an important role in the differentiation of naive precursors into T(h)1 or T(h)2 effector cells. To investigate the role of Jnk2 on autoimmunity, Jnk2(-/-) and wild-type mice were immunized with the myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide and the onset of EAE studied. Surprisingly, Jnk2(-/-) mice were as susceptible to EAE as wild-type mice, regardless of whether low or high antigen doses were used to induce disease. In vitro stimulation of lymph node cells from Jnk2(-/-) and wild-type mice resulted in comparable proliferation in response to MOG35-55, Mycobacterium tuberculosis and concanavalin A. MOG35-55-specific T cells lacking Jnk2 showed a T(h)1 cytokine profile with IFN-gamma, but no IL-4 or IL-5 production. No differences in the types of infiltrating cells or myelin destruction in the central nervous system were found between Jnk2(-/-) and wild-type mice, indicating that lack of Jnk2 does not alter the effector phase of EAE. Our results suggest that, despite involvement in T(h)1/T(h)2 differentiation in vitro, Jnk2 is necessary neither for the induction nor effector phase of MOG35-55-induced EAE and nor is it required for antigen-specific IFN-gamma production.