PRL receptor (PRL-R) expression has been analyzed in human hematopoietic tissues using flow cytofluorometric analysis with a series of biotinylated monoclonal antibodies (mAbs) directed against the extracellular domain of the rat liver PRL-R. In the thymus, more than 75% of cells were labeled by the anti-PRL-R mAb. Regarding PRL-R expression in the four T-cell subsets defined by CD4/CD8 expression, the majority of cells expressed low receptor levels, whereas a minority of double negative (CD4-CD8-) and single positive CD4+ cells were strongly labeled by the anti-PRL-R mAb. In the peripheral blood, an average of 80% of lymphoid cells, comprising all B-cells, all monocytes, and 75% of T-cells, were consistently PRL-R positive. Regarding T-cell subsets, similar percentages of PRL-R+ cells were observed in CD4+ and CD8+ peripheral lymphocytes (70-75%), and the density of labeling per cell was significantly lower than that occurring in B-cells or monocytes. Interestingly, the intensity of labeling significantly increased in peripheral T-cells after T-cell activation. The ubiquitous distribution of PRL-R in bone marrow stem cells, B-cells, monocytes, and T-cells was confirmed by the positive staining obtained in a set of human lymphoid cell lines. These data along with those showing that the PRL gene is specifically expressed in human T-cells suggest that lymphocyte PRL may act in a paracrine or autocrine fashion in both central and peripheral lymphoid organs.