We have initiated studies to evaluate the suitability of performing therapeutic conditioning trials in experimental autoimmune encephalomyelitis (EAE) mice treated with alpha lipoic acid (ALA). EAE was induced in SJL mice by active immunization with myelin antigen. Once daily subcutaneous injection of ALA served as the unconditional stimulus (US) administered with the conditional stimulus (CS) saccharin-flavored drinking water under a regimen of restricted water access. In the first study, we found that water restriction and saccharin administration were compatible with disease development and effective ALA treatment of EAE mice. In the second study, mice were conditioned to once daily administration of ALA paired with administration of saccharin-flavored water (US+CS) on days 7-16. Test trials spanned experimental days 17-32 in groups receiving either saccharin-flavored water (CS, in the experimental group) versus unflavored water (CSo, in the control group) and compared several measures of EAE severity using multivariate ANOVA (MANOVA). Reduced disease severity in the experimental group (US+CS:CS) compared to the control group (US+CS:CSo) suggested that conditioning had occurred. These results demonstrate an approach for conducting therapeutic conditioning trials in EAE mice and suggest considerations for future investigations.