The pro-neural achaete-scute complex (ASC) of Drosophila encodes four homologous proteins, each containing a basic helix-loop-helix (bHLH) domain, characteristic of a large family of transcription factors. We have isolated XASH1, a Xenopus homolog of achaete-scute. The XASH1 protein is very similar to the ASC proteins of Drosophila and the rat homolog, MASH1. XASH1 is expressed in the embryonic anterior central nervous system in a dynamic sequence, first in the midbrain, then in the forebrain, and then in the eye and hindbrain. In the larva, XASH1 expression correlates with regions of continued neurogenesis in the CNS, revealing the pattern of rhombomeres in the hindbrain, and other proliferative zones in the eye and midbrain. As a heterodimer with the bHLH protein E12, XASH1 binds specifically to an enhancer sequence derived from the promoter of the proneural achaete gene of Drosophila. This binding is inhibited by the extramacrochaete protein, a negative regulator of ASC gene function and neurogenesis in Drosophila. The combined evidence described in this paper strongly suggests that XASH1 plays a role in Xenopus neurogenesis similar to that played by the ASC genes in Drosophila.