Twelve patients with relapsing-remitting multiple sclerosis and 3 control subjects were evaluated weekly for six months. Peripheral blood lymphocyte subsets were enumerated using monoclonal antibodies and analysis with a dual-laser fluorescence-activated cell sorter. Results were correlated with clinically assessed disease activity. Fluctuations occurred in the number of T lymphocytes (Leu 1+) and cells with the helper/inducer phenotype (Leu 3a/OKT4+) in both patients and controls. Fluctuations in the number of cells with the suppressor/cytotoxic (Ts/c) cell phenotype (OKT5, OKT8, Leu 2a+) also occurred. Variations in the relative numbers of cells labeled with all three Ts/c monoclonals did occur, but with OKT5 generally labeling fewer cells than OKT8 or anti-Leu 2a. When findings were correlated with disease activity, OKT5 was a more sensitive gauge of disease activity than either OKT8 or anti-Leu 2a. When peripheral blood lymphocyte subsets were correlated with disease activity, the following patterns were observed: a reduction in the number of Ts/c cells without evidence of clinical disease (four episodes), the development of new symptoms suggestive of an acute relapse but without a reduction in the number of Ts/c cells (two episodes), and a reduction in the number of Ts/c cells associated with acute relapse (two episodes). In the two patients with acute relapse and a reduction in the number of Ts/c cells, clinical disease preceded a reduction in the number of Ts/c cells in 1 patient, whereas the two events occurred simultaneously in the other patient. Taken together, these limited results indicate that in some cases a reduction in the number of Ts/c cells may be the result rather than the cause of disease activity and may represent an epiphenomenon.