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Kaposi's sarcoma (KS), a condition often associated with HIV infection, is more common in men than in women; pregnancy and sex hormones could be involved. Urinary human chorionic gonadrotrophin (hCG) has been reported to inhibit the growth of KS cell lines, with great variability among preparations. Urinary hCG often contains free forms of the hCG subunits and a fragment of the free β-subunit, the β-core, which may have biological activity. We compared the effect of the β-core fragment, the β-subunit, recombinant and urinary hCG on KS immortal and spindle cells.A new immortal KS cell line was phenotypically and karyotypically characterized. The effects on growth of this cell line and of primary KS spindle cells by hCG and its purified derivatives were tested. Induction of apoptosis was demonstrated using acridine orange/ethidium bromide staining.The β-core fragment harboured the most potent growth inhibitory activity on a molar basis. After 72 h of treatment with the β-core, 60–70% of KS cells show apoptotic nuclei. No effects were observed on endothelial cells.The β-core fragment of hCG proved to be the most effective part of the hCG molecule, inducing growth inhibition and apoptosis of KS cells. Thus, the β-core could be the most appropriate hCG derivative for the therapy of KS.