Oligodendrocyte‐specific protein (OSP) is concentrated in CNS myelin and is a potential autoantigen in the development of multiple sclerosis (MS). We performed proliferation assays with lymphocytes from MS patients and normal controls. OSP peptide‐induced proliferation was common in relapsing‐remitting MS and controls samples but was less pronounced in samples from secondary progressive MS subjects. These data demonstrate that OSP‐reactive T cells are part of the normal immune repertoire and therefore have the potential to contribute to the pathogenesis of MS. Given the lack of specificity to MS, OSP‐reactive T‐cells are unlikely to be solely responsible for the disease process. J. Neurosci. Res. 66:506–509, 2001. © 2001 Wiley‐Liss, Inc.