Function and phenotype of peripheral blood (PB) T cells in multiple sclerosis (MS) patients were analyzed. In whole blood cultures, T cell proliferation of multiple sclerosis (MS) patients, using soluble CD3 mAb and CD2 mAb as stimulants, was reduced in comparison to healthy controls. A similar difference was seen when isolated PBMC were tested after stimulation with soluble CD3 mAb. However, in accessory cell-independent activation systems, i.e. after stimulation of PBMC with immobilized CD3 mAb or after co-stimulation with CD28 mAb, both patients and controls responded equally well. Phenotypical analysis of the circulating T cell population showed that there were no differences in the percentage of CD26+, 'memory' (CD45R0+) or 'effector' (CD4+CD45R0+CD27-) cells between MS patients and healthy controls. Finally, although MS patients did show an enhanced proportion of 'naive' (CD4+CD45RA+) T cells, this did not correlate with the observed functional defects.