We present here a model for the degradation of chromatin in cells undergoing apoptosis. This model rationalises all aspects of the fragmentation process that have been described to date, explaining not only the patterns of degradation seen within individual cells, but also the variability in extent of degradation seen in different cells. Although DNA fragmentation in apoptosis was initially considered to be solely internucleosomal, it is now apparent that the process is much more complex and most, if not all, cells also produce much larger DNA fragments. However, in the same way that internucleosomal DNA fragmentation is a reflection of chromatin structure, the generation of these larger fragments is a reflection of chromatin structure, too. By comparing the ionic requirements for the complete pattern of chromatin degradation in nuclei with those required for apoptosis, it is apparent that the whole process may be catalysed by two pools of Mg-activated\Ca-modulated DNase I-like enzyme activities.