Within the peripheral blood, CD4 +CD27 − T cells only reside within the CD45RAT −(memory or primed) T cell subset. Cells with this phenotype have characteristics of specialized effector T cells according to their cytokine secretion profiles and the expression of tissue-specific adhesion molecules. This subset was previously found to be increased in certain diseases that are associated with immune activation. Therefore we analyzed CD27 expression of peripheral blood and CSF T cells in MS patients. Within the CD4 + T cell subset no differences were seen between MS patients and controls in proportions of CD45RA −CD27 − cells. However, when the CD3 + T cell compartment was analyzed, CD27 − cells were also found within the CD45RA + subset. These cells, most likely CD8 +, are significantly reduced in PBL and CSF of MS patients as compared with OND patients. In MS and OND groups the level of CD27 − cells in peripheral blood correlated significantly with that in CSF, indicating a balanced migration of CD27 − cells between the two compartments. In OIND patients, however, this equilibrium was lost. The correlation of the level of CD27 + cells with the amount of intrathecally produced IgG in MS patients may suggest that CD27 + cells are responsible for B cell help in this disease.