The effect of the main pregnancy hormone, chorionic gonadotropin (CG), on proliferation of peripheral blood mononuclear cells (PBMC) was studied in the presence of autologous neutrophils; also, hormone-dependent regulation of the cAMP levels in T lymphocytes and neutrophils was evaluated. PBMC proliferation in response to a mitogen is suppressed by physiological doses of CG (10, 50, and 100 IU/ml). Autologous neutrophils enhance the suppression induced by the low dose of CG (10 IU/ml), but when cyclooxygenase was inhibited this effect was not observed; this suggests that the anti-proliferative effects of the low dose of CG can be mediated by the products generated by neutrophil cyclooxygenase. The effect of CG was associated with increased cAMP levels in T lymphocytes and neutrophils. Comparison of functional and cAMP-related effects of CG in both cell populations indicates that cAMP is involved in the anti-proliferative effects of CG.