Injection of Xenopus myoD mRNA into Xenopus embryos leads to only a modest activation of myogenic markers. In contrast, we show that injected mouse myoD mRNA leads to a potent activation. We postulate that XMyoD is under negative control in frog embryos, but because of slight sequence differences, mouse MyoD fails to see the negative signal. Whereas mMyoD is constitutively nuclear, XMyoD is largely cytoplasmic except in a region of the embryo that includes the location where mesoderm induction occurs; there, it is nuclear. At MBT, endogenous XmyoD mRNA is expressed ubiquitously in the frog embryo. Our results suggest that this expression would lead to cytoplasmic XMyoD protein. Among other events, muscle induction might remove this negative regulation, allow MyoD to enter the nucleus, and establish an autoregulatory loop that could commit cells to myogenesis.