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OBJECTIVE: To determine whether haematopoietic progenitor cells and erythropoietin (EPO), which is an essential humoral stimulus for erythroid progenitor (BFU-E) cell differentiation, are affected by lead intoxication. METHODS: In male subjects chronically exposed to lead with and without anaemia, pluripotent (CFU-GEMM), BFU-E and granulocyte/macrophage (CFU-GM) progenitor cell counts in peripheral blood were measured with a modified clonal assay. Lead concentrations in blood (PbB) and urine (PbU) were measured by the atomic absorption technique, and EPO was measured with a modified radioimmunoassay. RESULTS: PbB in the subjects exposed to lead ranged from 0.796 to 4.4 mumol/l, and PbU varied between 0.033 and 0.522 mumol/l. In subjects exposed to lead with PbB > or = 2.896 mumol/l (n = 7), BFU-E cells were significantly reduced (p < 0.001) whereas the reduction in CFU-GM cells was only of borderline significance (p = 0.037) compared with the age matched controls (n = 20). The CFU-GEMM cells remained unchanged. Furthermore, BFU-E and CFU-GM cells were reduced in a dose dependent fashion, with increasing PbB or PbU, respectively. In the subjects exposed to lead EPO was in the normal range and did not increase in the presence of anaemia induced by lead. No correlations existed between EPO and PbB, PbU, or progenitor cells. CONCLUSION: The data suggest new aspects of lead induced anaemia besides the currently acknowledged shortened life span of erythrocytes and inhibition of haemoglobin synthesis. Two additional mechanisms should be considered: the reduction of BFU-E cells, and inappropriate renal EPO production in the presence of severe exposure to lead, which would lead to an inadequate maturation of BFU-E cells.