We found that in vitro migration and interferon-gamma production by lymphocytes derived from primary progressive multiple sclerosis patients preselected on the basis of a high T2-weighted lesion volume (>10 cm3) on magnetic resonance imaging, were increased compared with that in primary progressive multiple sclerosis patients with a low T2-weighted lesion volume (<3 cm3) and controls. Whether the heterogeneity of immune function within the primary progressive population will correlate with response to therapy remains to be established.