Four patients with relapsing-remitting multiple sclerosis (MS) and one control were evaluated serially over a 10-week interval. Peripheral blood lymphocyte (PBL) subsets were enumerated using a double labelling technique, OKT5 and anti-Leu 2a monoclonal antibodies, and FACS IV analysis. Results were correlated with clinically assessed disease activity. Two subsets were identified. Subset 1 is characterized by cells positive for Leu 2a and either weakly positive or negative for OKT5 . Subset 2 was positive for both. Subset 1 was constantly present in both patients and controls while subset 2 was variable in presence and in size. No associations between these subsets and disease activity were made in this preliminary study, however, no acute relapses occurred in this interval. It is postulated that the reason for the differences in results of studies attempting to correlate disease activity with PBL phenotypes as assessed by different monoclonal antibodies may be the result of the suppressor/cytotoxic cell subpopulation being nonhomogeneous for the expression of various cell surface antigens. The technique of multiple labelling of lymphocytes may be useful in defining subsets which correlate more closely with disease activity.