Using indirect immunofluorescence and flow cytometry, we determined the proportion and number of T3+, T4+, and T8+ cells in the peripheral blood of patients with systemic lupus erythematosus whose sera were positive for cold-reactive antilymphocyte antibodies versus values in patients whose sera were negative for these antibodies. There was a disproportionate reduction in T4+ peripheral lymphocytes when cold-reactive antilymphocyte antibodies preferentially cytotoxic for this subpopulation were present in autologous serum. The decrease in this subset was responsible for a reduction in the T4:T8 ratio; variation in the number and proportion of T8+ cells was insignificant. A similar, but autoantibody-independent, alteration in the T4+ subpopulation was found in patients who were receiving prednisone therapy. A relationship between T cell population abnormalities and systemic lupus erythematosus disease activity, per se, was not observed.