Females have an increased incidence of multiple sclerosis (2:1). This gender dimorphism can be studied effectively using a murine model of relapsing experimental autoimmune encephalomyelitis (R-EAE). We demonstrated previously that male SJL mice immunized with proteolipid protein (PLP) peptide 139-151 developed an initial episode of paralysis, but failed to relapse. In the present study, clinical EAE relapses were induced by orchidectomy. Relapses in castrated mice were accompanied by an influx of activated CD4+, Th1 cells into the CNS which were absent in sham mice. Our data suggests an important regulatory role for androgens on the immune response to PLP 139-151 and the clinical course of R-EAE.