Tie, a new receptor tyrosine kinase, is expressed in vascular endothelial and hematopoietic cells. To determine whether Tie might be involved in early hematopoiesis, we asked whether the Tie gene is expressed in normal human hematopoietic stem/progenitor cells and if the expression of this gene could be regulated. Using a single-cell reverse-transcriptase polymerase chain reaction (RT-PCR) assay to study expression of the Tie gene in the subset of human umbilical cord blood (UCB) CD34+++ primitive stem/ progenitor cells with extensive replating capacity, we demonstrated at the single isolated cell level that Tie was expressed in these cells. The expression of Tie gene in CD34+ cells was at a low level but was enhanced up to two- to fourfold by steel factor (SLF) or leukemia inhibitory factor (LIF), two cytokines that regulate production of stem/progenitor cells, as assessed using competitive PCR and semi-quantitative RT-PCR assays. The fold increases were observed as early as 2 h for SLF and 4 h for LIF and remained elevated for 24 h. These results demonstrate modulation of gene regulation in the rare populations of CD34+ cells and suggest the possibility that Tie may play a role in the proliferation and differentiation of immature hematopoietic cells.