The authors studied mineralocorticoid receptor (MCR)-mediated effects of steroids on CD34(+) progenitor cells. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis showed the presence of mRNA for both the MCR and the alpha subunit of the epithelial sodium channel, a member of the amiloride-sensitive sodium channel (ASSC) superfamily, in human CD41(+) megacaryoblastic cells derived from cultured bone marrow CD34(+) isolates, as well as in the human erythromegakaryoblastic leukemia (HEL) cell line. Immunofluorescence also revealed the presence of both the MCR and ASSC in circulating CD34(+) and medullar CD41(+) megacaryoblastic cells, the former as a nucleocytoplasmic protein and the latter as a membrane-bound protein, as expected from earlier studies using MCR-specific targets. In a selective medium, the formation of erythrocyte burst-forming units, and of the granulocyte-macrophage colony-forming units, by circulating CD34(+) cells was influenced by the agonists deoxycorticosterone and aldosterone, as well as by the antagonists RU 26752 and ZK 91587, targeted for the MCR. The multiplication of the leukemic HEL progeny, derived from CD41(+) cells, was similarly altered by these steroids targeted for the MCR. In contrast, in the optimal growth medium, the multiplication, and colony formation by bone marrow CD34(+) progenitor cells were not altered by either aldosterone or ZK 91587. These and other studies reveal that the receptor-mediated action of mineralocorticoids may influence the functional maturation of the hematopoietic progenitor lineage, contrary to the classical notion where the mineralotropic effect would be a unique feature of the epithelial cell.