Maternal immunologic recognition of the blastocyst as well as the hormone chorionic gonadotropin (CG) has been shown to be a requirement for successful implantation of the blastocyst and maintenance of the fetal graft. On the basis of these observations, we tested whether lymphocytes could produce chorionic gonadotropic-like hormones during a mixed lymphocyte reaction (MLR). Here we describe the production of immunoreactive chorionic gonadotropin (ir-CG) as a result of an allogeneic stimulus but not other mitogenic stimuli. The kinetics of production, as monitored by immunofluorescence with antibody specific to the (3 chain of the human CG (hCG) molecule, paralleled the blastogenic response. Gel ifitration of the de novo-synthesized ir-CG showed the molecular weight of the intact molecule to be approximately 58,000. This molecule bound to a concanavalin A affinity column and also dissociated into two subunits of approximate molecular weights 32,000 and 18,000. These molecular weights are consistent with reported molecular weights for glycosylated intact hCG, as well as the ( and a chains of hCG, respectively.The material from the MLR but not the control cultures elicited Significant testosterone production from Leydig cells, and this activity could be blocked by antiserum to hCG. The results described here, together with the fact that the blastocyst is implanted in a lymphocyte infiltrate, lend support to our postulate that lymphocyte-derived CG enhances successful implantation of the allogeneic fetus, thus providing a mechanism for selection of genetic diversity.Unlike other tissue grafts, the fetal graft depends on maternal immune recognition of the graft as foreign for its success. This recognition is subsequently followed by the production of blocking and suppressor factors, which allows for implantation and prevents rejection of the fetal graft (for review, see ref. 1). The more similar the major histocompatibility complex (MHC) of the male and female parents, particularly in the D/DR region, the lower the frequency of implantation and the greater the likelihood of recurrent spontaneous abortion (for review, see ref.2). In fact, spontaneous abortion has been prevented 'by vaccination of the females with leukocyte MHC antigens (3). In the syngeneic mouse system, several elegant studies have shown that shared histocompatibility between mother and conceptus results in a reduction of litter size and elimination of 50% of the grafts in 2-3 weeks (reviewed in ref. 4).It has been proposed that the basis of the allogeneic recognition by maternal lymphocytes is the trophoblast lymphocyte-crossreactive antigen (TLX) system (5). Numerous studies have shown that these antigens are allotypic and polymorphic and are present on the surface of peripheral blood lymphocytes and the blastocyst (trophoblastic cells). Antisera to these antigens inhibit the mixed lymphocyte reaction (MLR), and the antigens have been postulated to be closely linked to the human leukocyte antigen (HLA) or MHC locus (for review, see ref....