We identified gender related differences of inducible nitric oxide synthase (iNOS) expression and NO production in mice with experimental autoimmune encephalomyelitis (EAE). When myelin basic protein-specific T-lymphocytes derived from female mice were transferred, the female recipients developed more severe EAE and expressed higher levels of iNOS and NO than male recipients. When the T-lymphocytes derived from males were transferred, severe EAE was induced in neither female or male recipients and neither iNOS nor NO were detectable. These data show an association between No production and EAE severity, suggesting a possible role of NO in the pathogenesis of EAE.