BACKGROUND: Somatostatin (SS)-binding sites have been demonstrated in human lymphoid tissues and peripheral blood cells. However, not much is known with respect to the SS receptor subtype (sst) expression pattern and the expression of SS itself in the immune system. OBJECTIVE: The aim of this study was to evaluate the mRNA expression of the five known sst (sst(1-5)) in peripheral blood mononuclear cell (sub)populations. Moreover, the expression of the mRNAs encoding SS and the SS-like peptide cortistatin (CST) in immune cell subsets was studied. METHODS: RT-PCR and quantitative PCR were performed to evaluate sst, SS and CST mRNA expression in cells in the basal or activated state. Fluorescence-activated cell sorter (FACS) analysis using fluorescent SS was performed to visualize sst protein on cell membranes. RESULTS: B- and T-lymphocytes selectively expressed sst(3) mRNA. sst(3) expression in B-lymphocytes was significantly lower compared with T-lymphocytes. Unstimulated, freshly isolated monocytes did not express any sst mRNA. Upon activation, monocytes selectively expressed sst(2) mRNA, whereas T-lymphocyte activation upregulated sst(3) expression. sst(2) mRNA expression on monocytes was confirmed by FACS analysis. B- and T-lymphocytes did not express SS mRNA, while both cell types expressed CST mRNA. CST mRNA expression was downregulated following T-lymphocyte activation. CONCLUSION: We demonstrate for the first time unequivocally that human peripheral blood B- and T-lymphocytes selectively express sst(3), whereas monocytes do not express sst. However, upon activation, monocytes are induced to express sst(2A). No expression of SS mRNA was detected in any cell type, whereas all cell types expressed CST mRNA. The differential expression of sst and CST mRNA in lymphocytes and monocytes suggests a functional significance for the CST-sst interaction in immune cells, but further studies should be performed to evaluate the significance of sst and CST in these cells.