To investigate the pathophysiology of anemia, a two-color flow cytometric method was developed that measures the proliferative rate of the marrow erythroid cells (EPR). The method uses a monoclonal antibody, RC17.2, to identify erythroid precursors and propidium iodide to determine the %S-phase. This technique was then used to test the hypothesis that a decrease in the proliferative rate of the marrow erythroid precursors contributes to the anemia of multiple myeloma. The EPR was determined on the marrow aspirate from 56 patients and the mean EPR was 31.2% (median, 31: range, 14-55). Patients with anemia (n = 36) had a median EPR of 27% compared to 35% for those patients with a normal Hgb (p = < 0.001); however, there was no difference in the % marrow erythroid precursors (p = 0.96) or % marrow plasma cells (p = 0.08) between the two groups. These results suggest that one possible cause for the anemia of myeloma is a decrease in the EPR. This flow cytometric technique may also be useful in studying other anemias.