We have investigated whether human lymphoid cells are able to synthesize and secrete human PRL (hPRL) and to express PRL receptors. Metabolic labeling with [35S]methionine and immunoprecipitation of cell extracts from human mononuclear cells (MNC) and a human T lymphocyte cell line with an antiserum against hPRL revealed protein of M(r) 23,000, identical in size to pituitary hPRL. Dilution curves of lymphocyte immunoreactive hPRL were parallel to those obtained with pituitary hPRL in an immunoradiometric assay using two monoclonal antibodies against hPRL. Polymerase chain reaction experiments with primers located in the coding sequence of hPRL showed that the hPRL gene was expressed in MNC. Furthermore, cDNA cloning and sequence analysis indicated the presence of an extra 5' noncoding exon previously described for decidual hPRL. When MNCs were further separated into B cells, T cells, and monocytes, the expression of hPRL appeared to be mainly associated with the T lymphocyte fraction. The hPRL transcript was also detected in thymocytes and in a set of human lymphoid cell lines. Finally, polymerase chain reaction experiments revealed a ubiquitous distribution of PRL receptor gene expression in B cells, T cells, and monocytes. The presence of the receptor for PRL and production of PRL by T lymphocytes suggest a possible autocrine or paracrine effect of PRL in immune cell function.