The product of the c-myc oncogene is an important regulator of both cell proliferation and programmed cell death (apoptosis). We have previously shown that a myelomonocytic cell line termed tEMmyc4, with enforced v-myc expression, underwent apoptosis under growth inhibitory conditions. To further investigate the linkage of v-myc expression to apoptosis in these cells, two hammerhead ribozymes were designed and shown to specifically cleave the v-myc though not c-myc transcript in vitro. These ribozymes were then engineered into the pMAMneo vector under the control of MMTV promoter, transfected into tEMmyc4 cells and clonally selected in G418. Molecular analysis revealed reduction of v-myc expression in ribozyme-expressing cells. This reduction was shown to be associated with abrogation of hormone-induced apoptosis (monitored by gel electrophoresis, flow cytometry and TUNEL assay). These results confirm a direct involvement of v-myc in the induction of apoptosis and indicate a potential means to molecularly control apoptosis using a ribozyme-targeting approach.