The proliferative potential of multinucleated Reed-Sternberg-like cells and the process of multinuclear formation were studied on the Hodgkin's-disease-derived cell line HDLM-2. No difference in surface antigen expression was found between mono- and multinucleated cells as determined by immunolabelling with characteristic markers. After sorting and reculture of purified mononucleated cells, polykaryons emerged subsequently in these cultures, indicating that mononucleated cells give rise to multinucleated variants. The morphological observation of mitotic figures and immunostaining with the cell cycle indicators Ki-67 and BrdU provided evidence of DNA synthesis and nuclear division in multinucleated cells. The presence of mitotic figures demonstrated that multinucleated cells are able to undergo synchronous nuclear division. However, while polykaryons were clearly mitotically active and capable of DNA synthesis, the absence of telophases and the failure of active replication suggest a disturbed cytokinesis. Co-cultivation of BrdU-labelled and unlabelled populations did not lead to hybrid polykaryons with negative and positive nuclei. Therefore, multinucleated giant cell formation of HDLM-2 cells appears to involve nuclear endomitosis without cell division rather than cell fusion.