Tissue culture of six human giant cell tumors of bone was undertaken (one on two occasions). All of them were cultivated successfully. Five cultures have shown outgrowth in about 25 days. In the remaining two cases continuous culture (nine generations) was successfully carried out. From this study the following results were obtained: the giant cells usually persist for about 48 to 72 h in primary tissue cultures. New giant cells were born during the following days in vitro. In trypsinized material the two cultures obtained lost their primitive growth features after the second generation. However, the ability to form giant cells is not definitely lost as is demonstrated by organ culture technique. The multinucleated giant cells exhibit, in primary tissue cultures, the same cytological and cytochemical features as normal osteoclasts and giant cell tumors. The mechanism of giant cell formation seems to be direct amitotic division, fusion of two or more mononuclear cells, or a combination of both. Furthermore, it was possible to detect a resting nucleus and another nucleus in mitotic division, side-by-side in the same cell, an unusual phenomenon in cell biology.