In the present study, we evaluated whether mononuclear leukocytes could synthesize and secrete growth hormone (GH) in vitro. Studies using antibody affinity chromatography, high pressure liquid chromatography, and polyacrylamide gel electrophoresis indicate that leukocytes secrete a ∼22,000 dalton molecular weight immunoreactive GH (irGH). The irGH appeared to be de novo synthesized since it could be radiolabeled with tritiated amino acids and its production blocked by prior incubation of leukocytes with cycloheximide. The levels of secreted irGH were enhanced by concanavalin A or lipopolysaccharide. By using RNA slot blot analysis, we detected specific GH mRNA present in the cytoplasm of rat leukocytes. Leukocytes from a variety of tissues in rats, including spleen, thymus, bone marrow, and peripheral blood as well as separated spleen T and B cells, were all observed to produce GH RNA and secrete GH from the cells. We conclude that lymphocytes produce a mRNA for irGH and are then able to translate that message and secrete the molecule from the cell. The data suggest a potential regulatory loop between the immune and neuroendocrine systems. © 1989 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.