The first step in the homing of hematopoietic progenitor cells (HPCs) from the peripheral blood to the bone marrow involves an adhesion molecule-dependent contact with human bone marrow endothelial cells (HBMECs). In the present study we describe the constitutive expression of two of these molecules, E-selectin and vascular cell adhesion molecule-1 (VCAM-1), on endothelial cells of hematopoietic tissues. Immunophenotypic analysis of tissue sections of hematopoietically active (human adult and fetal bone marrow, fetal spleen, fetal liver, and adult spleen with extramedullary hematopoiesis) and inactive tissues (human adult spleen, lymph node, appendix, and liver; and fetal lung and fetal intestine) revealed that E-selectin and VCAM-1 are selectively expressed on endothelial cells of adult and fetal hematopoietic organs. These results were validated by means of reverse-transcriptase polymerase chain reaction. Adhesion studies revealed that binding of normal mobilized peripheral blood HPCs to HBMECs was completely inhibited by preincubation of HBMECs with anti-E-selectin (ENA2), whereas no effect of anti-VCAM-1 (1G11B1) was detected. These results suggest that E-selectin plays a role in the homing of HPCs and that its constitutive expression on endothelial cells of hematopoietic organs may be essential in the initial step of the homing process.