To explore how S1P1 deletion would impact disease onset and progression, we induced experimental autoimmune encephalomyelitis (EAE) by immunization with myelin oligodendrocyte (MOG35–55) peptide emulsified in CFA (Complete Freund’s Adjuvant) after acute deletion of S1P1 with four consecutive tamoxifen injections. This evidence concerns the gene S1PR1 and experimental autoimmune encephalomyelitis.