Members of the myc family of cellular oncogenes have been implicated as transcriptional regulators in pathways that govern cellular proliferation and death. In addition, N-myc andc-myc are essential for completion of murine embryonic development. However, the basis for the evolutionary conservation ofmyc gene family has remained unclear. To elucidate this issue, we have generated mice in which the endogenous c-myccoding sequences have been replaced with N-myc coding sequences. Strikingly, mice homozygous for this replacement mutation can survive into adulthood and reproduce. Moreover, when expressed from the c-myc locus, N-myc is similarly regulated and functionally complementary to c-myc in the context of various cellular growth and differentiation processes. Therefore, themyc gene family must have evolved, to a large extent, to facilitate differential patterns of expression.