Patients with cytopenias and a cellular bone marrow can be a diagnostic and a therapeutic challenge. Previous reports have suggested a role for progenitor assays as a potentially useful test for diagnosis and predicting response to therapy. Here we report the results of BFU-E assays in 48 consultative cases of single or multi-lineage cytopenias with cellular marrows. The final diagnoses included 17 patients with myelodysplastic syndrome (MDS); 9 patients with pure red cell aplasia (PRCA) [non-large granular lymphocytosis (LGL) in etiology]; 15 patients with LGL (8 of which had a single lineage cytopenia only while the other 7 had multi-lineage cytopenias); and 7 patients with cytopenias associated with systemic inflammation related to autoimmune conditions. In this cohort, nonmalignant diseases were well-distinguished from MDS by BFU-E growth. Our data suggest that low BFU-E growth (less than 10 BFU-E /10(5) marrow mononuclear cells) helps to exclude LGL, PRCA, or cytopenias associated with systemic inflammation as a cause of pancytopenia with a sensitivity of 96.8%, specificity of 76.5% and a predictive value of 88.2% (p=0.0001). BFU-E growth was also examined to predict response to treatment. Of the 29 patients in this cohort treated with immunosuppressive therapy across all disease groups, there was an 86% response rate with 25 responders (11 PRs and 14 CRs) and 4 non-responders. This did correlate with higher BFU-E growth. Our results suggest BFU-E assays are a useful adjunct in the diagnosis and management of cytopenias in the setting of a normocellular or hypercellular bone marrows.