In a number of cellular systems, DNA in apoptotic cells is initially degraded into large fragments of 30-50, 200-300 and greater than or equal to 700 kilobase pairs, which may subsequently give rise to oligonucleosomal fragments often considered as the biochemical hallmark of apoptosis. In this study, necrosis was induced in U937 cells by incubation with water. Cells yielded large DNA fragments similar in size to those found in apoptosis, but the DNA was then degraded to a continuous spectrum of small fragments, confirming that death was necrotic. The results demonstrate that kilobase pair DNA fragments are formed in some instances of necrosis as well as in apoptosis. This indicates that apoptosis should not simply be assessed by the formation of kilobase pair DNA fragments, but that other criteria, such as cellular morphology, must also be used to verify apoptosis. (C) 1995 Academic Press, Inc.