In the murine interleukin 3 (IL-3)-dependent myeloid cell line 32D, down-regulation of c-myc and ornithine decarboxylase (ODC) expression is an immediate response to IL-3 deprivation. This is followed by an accumulation of cells in the G1 phase of the cell cycle, and eventual cell death. However, clones of 32D cells harboring an expression vector which constitutively expresses murine c-myc did not down-regulate ODC transcripts in response to IL-3 withdrawal, and they failed to G1 arrest. Moreover, in contrast to control cultures in which the majority of death occurred following G1 arrest, c-myc clones rapidly initiated a program of cell death characteristic of apoptosis following IL-3 deprivation, and their subsequent loss of viability occurred with accelerated kinetics. The premature induction of apoptosis in cells harboring a deregulated c-myc gene suggests that apoptosis may be an important mechanism in the elimination of hematopoietic cells harboring mutations, such as constitutive c-myc expression, which imbalance normal cell cycle regulatory controls.