Methotrexate (MTX) was covalently bound to rabbit antibodies (IgG) against hCG and placental alkaline phosphatase (PLALP) by two different methods. By carbodiimide method, 16.9 mols of MTX could be coupled to one mol of IgG, but the antibody activity was completely lost. Whereas, 2.6-3.4 mols of MTX were bound to one mol of IgG and a quarter of original antibody activity was preserved by dextran bridge method. Choriocarcinoma cells BeWo and SCH were exposed to the IgG-MTX conjugates prepared by the latter method for 30 minutes, and the cell growth was investigated. To BeWo, which produces much hCG and less PLALP, anti hCG-IgG-MTX showed a considerable growth inhibition compared to the control groups (p less than 0.05). No effect was observed with anti PLALP-IgG-MTX, nonimmunized IgG-MTX, free MTX and anti hCG-IgG. In contrast, to SCH, which produces much PLALP and less hCG, anti PLALP-IgG-MTX exhibited considerable inhibition (p less than 0.05), whereas anti hCG-IgG-MTX showed no inhibition. Neither anti hCG-IgG-MTX nor anti PLALP-IgG-MTX showed any effect to the endometrial carcinoma cell HEC50B. We concluded that MTX bound to anti hCG-IgG and anti PLALP-IgG have specific growth inhibition effects to the choriocarcinoma cells in vitro, and suggested the possibility of specific immunochemotherapy of this disease.