We have injected XIHbox 6 mRNA together with the lineage tracer colloidal gold into individual dorso-anterior blastomeres of the 32-cell stage Xenopus embryo and analyzed their cell fate during embryogenesis. While the developing tadpoles appeared entirely normal, the fate of the progeny of the injected blastomere was altered. In the brain injected cells failed to differentiate terminally, as indicated by a loss of labeled cranial nerves. Differentiation of spinal nerves remained unaffected. Fate change in the CNS occurred at about the time of normal XIHbox 6 protein expression. In addition, progeny of injected blastomeres gained head epidermal fate and lost anterior notochord fate as a result of altered cell migrations during gastrulation. The results show that a homeodomain protein is capable of altering cell fate in a position-specific and cell-autonomous manner in Xenopus embryos. The experimental approach used here should be applicable to other molecules specifying cell fate.