Apoptotic cell death has been correlated to DNA fragmentation into discrete segments corresponding to the length of nucleosomal protected fragments of 180-200 base pairs or multiples of it, This DNA degradation has been ascribed to endonuclease activity that cleaves internucleosomally, thus giving rise to a ladder distribution upon electrophoretic migration. This strict correlation was, however, shown to have notable exceptions, since in some cases only single strand cleavage in the internucleosomal DNA regions has been observed (Tomei, D. L,, Shapiro, P, J,, and Cope, O. F. (1993) Proc, Natl. Acad. Sci, U. S. A. 90, 853-857), In the present work we show that mouse muscle cells, able to differentiate in vitro, if subjected to apoptosis present no DNA degradation into ladder form unless differentiation is previously induced. Furthermore, C3H/10T1/2 fibroblast cells, known to undergo apoptosis without DNA ladder formation, if converted to a myogenic program by MyoD expression, display internucleosomal DNA degradation upon induction of differentiation.