The protooncogene c-myc positively regulates cell death in most in vitro cell model systems under conditions of restricted proliferation, and it has been proposed that cell death is a physiological function of c-myc. To investigate possible changes in c-myc expression concomitant with programmed cell death, we have analyzed c-myc mRNA expression during chick limb development. Expression of c-myc was high in the premuscular masses at earlier stages and in the chondrogenic condensations at later stages of limb development, as demonstrated by in situ mRNA hybridization in sections and whole-mount. However, we did not detect c-myc expression in specific limb areas where massive apoptosis was occurring. Furthermore, when the apical ridge was removed from stage 20 wing buds, there was no increase in the expression of c-myc in the subridge mesoderm, despite the extensive cell death induced by this surgical manipulation. Therefore, our results show no correlation between elevated c-myc expression and either programmed or experimentally-induced apoptosis in the developing limb. These results argue against a role of c-myc in cell death occurring in vivo.