Apoptosis plays an important role in the survival of an organism, and substantial work has been done to understand the signaling pathways that regulate this process. Characteristic changes in chromatin organization accompany apoptosis and are routinely used as markers for cell death. We have examined the organization of chromatin in apoptotic PC12 and HeLa cells by indirect immunofluorescence and electron spectroscopic imaging. Our results indicate that de novo chromatin condensation normally seen during mitosis does not occur when cells undergo apoptosis. Instead, the condensed chromatin typically observed results from aggregation of the heterochromatin. We present evidence that, early in apoptosis, there is a rapid degradation of the nuclease-hypersensitive euchromatin that contains hyperacetylated histones. This occurs coincident with the loss of nuclear integrity due to degradation of lamins and reorganization of intranuclear protein matrix. These events lead to collapse of the nucleus and aggregation of heterochromatin to produce the appearance of condensed apoptotic chromatin. This heterochromatin aggregate is then digested by nucleases to produce the oligonucleosomal DNA ladder that is a hallmark of late apoptosis. Unlike mitosis, we have not seen any evidence for the requirement of phosphorylated histones H1 and H3 to maintain the chromatin in the condensed state.