Three modes of activation of apoptosis are described: induction, in which new gene expression occurs after the stimulus is applied; transduction, in which gene expression is unnecessary at the time of stimulation; and release, in which apoptosis is activated by the inhibition of gene expression. Genes activated in the induction mechanism were identified by a process of subtractive hybridization, whereby newly transcribed messenger RNAs could be isolated. Progress in characterizing some of these genes is described. There are many difficulties and conceptual problems associated with such a gene cloning approach, but the results will be worth the effort.