Trisomy 21 is associated with high maternal serum concentrations of intact human chorionic gonadotrophin alpha(HCG) and free beta-HCG whereas these concentrations are markedly decreased in trisomy 18. In this study, we investigated the effect of trisomy 21 and 18 on endogenous HCG concentrations and luteinizing hormone (LH)/HCG receptor expression in placental villous tissue in eight trisomy 21, six trisomy 18 and 42 chromosomally normal samples, collected at 12-16 weeks gestation. The tissue concentrations of intact HCG, free alpha-HCG and free beta-HCG subunits were measured using solid-phase two-site immunoradiometric assay. LH/HCG receptor expression was evaluated with immunohistochemistry and in-situ hybridization. Villous tissue in trisomy 21 contained higher beta-HCG concentrations than the controls (P < 0.05). In trisomy 18 cases, the beta-HCG concentration was lower than in the control group (P < 0.01). Both immunocytochemistry and in-situ hybridization demonstrated a more intense staining of the trophoblast in cases of trisomy 21 and 18, compared with controls with the strongest signal in cases of trisomy 18 (P < 0.01). We concluded that in trisomy 21 the high tissue HCG concentration and expression of LH/HCG receptor in the trophoblast may reflect the relative immaturity of the trophoblastic tissue whereas in trisomy 18, the very low concentration of endogenous HCG, associated with an over-expression of LH/HCG receptor in the trophoblast, is probably secondary to the poor differentiation of the cytotrophoblast.