Lymphocyte subpopulations were studied by immunofluorescence staining with monoclonal antibodies and laser flow cytometry in the blood of 23 hemodialysis patients before and after 3 months of treatment with recombinant human erythropoietin (rhEPO). Correction of anemia was accompanied by an increase in natural killer cells and a decrease in B lymphocytes. In the 11 patients (Group 1) with a baseline helper/suppressor (T4/T8) ratio greater than or equal to 2, the latter significantly decreased from 3.0 +/- 0.3 to 2.1 +/- 0.3 through both an increase in T8 cells and a decrease in T4 cells (p less than 0.005). Among the 12 patients with a pre-EPO T4/T8 ratio less than 2 (Group 2), no difference in T cell subsets was observed. The decrease in ferritin levels observed over the study period was not significant. In addition, the mean increase in hemoglobin levels during the first month of rhEPO therapy was greater in Group 2 than in Group 1 (1.1 +/- 0.3 vs. 0.6 +/- 0.3 g/dl, p less than 0.025). No change in any parameter was observed in eight control patients not receiving rhEPO. These results suggest that rhEPO can induce changes in lymphocyte subpopulations of hemodialysis patients through mechanism(s) yet to be clarified; conversely, the T4/T8 ratio might be a predictive factor for the erythropoietic response to rhEPO.