Choriocarcinoma cells produce excessive amounts of hCG. However, it has never been questioned, to our knowledge, why these tumors produce such high levels in the first place. We hypothesize that these tumors produce such high hCG levels because they may be needed for their growth and development. In such a case, a dramatic reduction of hCG synthesis should have anti-tumor effects. We used antisense expression technology to test this hypothesis on human choriocarcinoma JAr cells, which like their tumor counterparts, secrete very high levels of hCG due to a loss of self-regulation. In this approach, we stably transfected JAr cells with a pRSV-anti-hCG-α subunit cDNA construct which transcribes antisense hCG-α subunit mRNA. The antisense hCG-α subunit mRNA will form a duplex with sense hCG-α subunit mRNA, blocking its translation into protein and, consequently, heterodimer hCG protein could not be made. The transfections resulted in: 1) a dramatic reduction in steady state hCG-α subunit mRNA and dimer hCG protein levels; 2) an increase in apoptosis; 3) a decrease in in vitro cell invasion in Matrigel membranes; and 4) decreased incidence of tumor formation in immunodeficient athymic intact female nude mice. Thus, these findings support our hypothesis that high hCG levels produced by choriocarcinoma cells may promote their growth and development in the host body.