The closely related homeodomain containing genes, Phox2a and Phox2b, are essential for neuronal specification and differentiation within discrete subsets of neurons during vertebrate embryogenesis. We have isolated Xenopus Phox2 homologs, termed Xphox2a and Xphox2b, and characterized their expression during early development. In addition, we have characterized a Phox2a splice variant, termed Xphox2a.2, which lacks homeo- and C-terminal protein coding domains. Xphox2a, Xphox2a.2 and Xphox2b transcripts are expressed in dynamic temporal and regional patterns during nervous system development. The expression of Xphox2a and Xphox2b is only partially overlapping and includes cranial motor and interneuron populations as well as peripheral sympathetic and cranial ganglion neurons, sites linked to Phox2 expression in other species. In addition, we have identified an early domain of Xphox2a and subsequent Xphox2b expression in ventral regions of the embryo, within the developing heart field. XPhox2 expression within this domain is preceded by the gastrula-stage expression of the proneural basic helix-loop-helix transcription factor, Xash1, pointing to a new region of action for this group transcription factors during vertebrate development.