BACKGROUND AND OBJECTIVE: Hypoplastic myelodysplastic syndromes (MDS) are being reported with increasing frequency. Aplastic anemia (AA) needs to be differentiated from hypoplastic MDS particularly primary hypoplastic refractory anemia (PHRA) because of the impact on management and prognosis. This distinction may be morphologically difficult even with careful marrow examination which may provide insufficient material due to extreme hypocellularity. The value of peripheral blood (PB) parameters in making the distinction between AA and PHRA is not well studied. In this work, we attempt to examine peripheral blood findings as an additional tool for differentiating PHRA from acquired idiopathic AA. METHODS: PB findings in ten cases of PHRA, which are selected based on the following: less than 30% cellularity, multilineage dysplasia and/or clonal cytogenetic abnormality, are compared to ten cases of classic AA. The PB is examined for automated parameters, differential white cell count, morphologic changes in red cells, white cells, platelets, and the presence of circulating blasts, megakaryocytic fragments and micromegakaryocytes. RESULTS: AA patients tend to have lower platelet and monocytic counts and higher lymphocytic percentages. The following morphologic findings are seen only in PHRA but not in AA: hypochromic red cells, left shift, circulating blasts, hypersegmentation with long filaments, hypogranular, ring, and pelgeroid neutrophils, Dohle bodies, circulating micromegakaryocytes and megakaryocytic fragments. INTERPRETATION AND CONCLUSIONS: We conclude that careful examination of peripheral blood may provide sufficient information to allow for the distinction between PHRA and AA early in the course of the disease. Similarly, patients with classic AA who subsequently develop unusual blood findings during routine follow up should be suspected of having a clonal evolution which needs to be confirmed by marrow examination and cytogenetic analysis.