Abnormalities of T-cell subsets in patients with multiple sclerosis are well known; in order to assess whether immunological abnormalities are relevant in the pathogenesis of the disease after its clinical onset, peripheral blood lymphocyte subsets (CD3+, CD4+, CD4(+)-CD45RA+, CD4+CD45RA-, CD8+, CD8+CD57+, CD57+, CD25+) were analysed serially in 25 patients at the first clinical episode suggestive of inflammatory demyelinating disease and in an equal number of age- and sex-matched controls. During the follow-up period (12-18 months, mean 14) 6 of 25 patients presented new relapses: in this subgroup of patients, significant changes in CD4+ ratio (% CD4+CD45RA-/%CD4+CD45RA+) were detected in comparison both with healthy controls and with clinically stable patients. Patients clinically stable at follow-up did not display immunological abnormalities, regardless of the presence or absence of cerebrospinal fluid and/or magnetic resonance imaging alterations consistent with multiple sclerosis. These findings suggest a possible prognostic role of early T-cell subset imbalance in multiple sclerosis.