Here we report our experience in profiling peripheral blood T-cell subsets with the monoclonal antibodies OKT4, OKT5 , and OKT8. Lymphocyte surface phenotype was measured by automated cytofluorometry. In a population survey, we were unable to detect differences between patients with multiple sclerosis (MS) and control subjects when we compared ratios of lymphocytes of helper cell phenotype (OKT4) to those with suppressor cell phenotype ( OKT5 and OKT8). No differences could be established between patients with stable disease, chronic progressive disease, or those with active disease. In a study of 10 patients followed through an exacerbation, we were also unable to define perturbations in these lymphocyte ratios that correlated with disease activity. Detailed analysis of the fluorescence histogram, which examines the entire spectrum of cell surface fluorescence intensity in a population of lymphocytes, was also not useful in predicting disease activity in these patients. The discrepancies between these data and other reports in the literature are discussed. We propose that these reagents are inadequate indices of disease activity, and that until other monoclonal reagents are developed and studied, the suppressor cell compartment is best assessed by assays of function.