This study reports on neuropeptide Y (NPY) mRNA expression in human peripheral blood mononuclear cells (PBMC) and lymphoid tissues. By reverse transcription polymerase chain reaction (RT-PCR) it is shown that activated human PBMC of normal blood donors expressed the NPY gene. The PCR products had the expected size and Northern blotting demonstrated the presence of the 0.8-kb NPY mRNA. To define the subpopulations of mononuclear cells expressing this neuropeptide, purified monocytes, B cells and T cells were stimulated with specific activators. Monocytes and in vitro matured macrophages expressed NPY mRNA in response to phorbol myristate acetate (PMA). B lymphocytes expressed NPY mRNA following stimulation with antibody to surface immunoglobulin and PMA. In order to analyze whether these cell types express NPY under physiological conditions in vivo, human bone marrow, tonsil and thymus were analyzed. In situ hybridization of bone marrow revealed a small number of cells containing high levels of NPY mRNA which was also detected in RNA extracts of human thymus and tonsil. In summary, NPY is an inducible gene in human lymphocytes and monocytes and it is expressed at sites where these cells are activated in vivo.