This study was designed to examine the viability and proliferation of uninucleated and multinucleated giant cells formed after 6 Gy X irradiation. The pedigrees of 102 individual EJ30 giant cells present 5 days after irradiation were analyzed from time-lapse movies captured over 6.3 days from 100 fields (100x). Pedigree analysis enabled us to study the proliferation of giant cells. The average starting size (area) of the giant cells (14500 +/- 9100 microm(2)) was approximately 25 times larger than the normal-sized cells observed after irradiation (560 +/- 200 microm(2)). From a total of 76 pedigrees of uninucleated giant cells, 42 had giant cells that either died or were arrested, while 34 divided at least once and produced progeny that divided again (five three times and three four times) before the progeny died or were arrested. Twenty-four pedigrees contained progeny that were lost from observation after dividing at least once. While most progeny continued to have giant cell morphology, two uninucleated giant cells ultimately produced progeny that contained two normal-sized cells. From a total of 26 multinucleated giant cells, only three divided. Two divided only once, but one produced progeny that divided two times. In all, 37 out of 102 giant cells divided at least once; eight of these divided four or five times with two of these pedigrees ultimately producing two normal-sized daughter cells. These results suggest that a small fraction of giant cells might be potentially clonogenic.