Apoptosis is an active form of cell death which plays an important role in different biological processes. The induction of apoptosis usually requires de novo gene expression but has also been observed in certain types of cells in absence of gene expression or following a block of gene expression. We show here that inhibition of macromolecular synthesis induced the rapid apoptotic death of most antibodysecreting B-cell hybridomas. The effect was observed in presence of both protein synthesis (cycloheximide [CHX]) and transcription (actinomycin D [Act D]) inhibitors and was characterized by extensive degradation of nucleic acids (DNA and RNA) within 2-3 h of treatment. The CHX treatment not only severely impaired the proliferation of the cells but also resulted in the loss of cell viability (MTT assay) without the need of de novo gene expression. The susceptibility to apoptosis varied among different B-cell hybridomas and was inherited from the SP2/O myeloma cell fusion partner. These results indicate the constitutive activation of a death program in B-cell hybridomas and its inhibition at a late stage by the continuous expression of gene(s) coding for short-lived protein(s). The occurrence of this phenomenon may well be related to the abundant and deregulated (translocation) expression, in this type of cells, of the c-myc gene which has recently been shown to be a potent inducer of apoptosis in growth-arrested fibroblasts.