We have isolated an amphibian homolog of the homeotic gene spalt of Drosophila. Like its Drosophila counterpart the Xenopus Xsal-1 gene encodes a protein that contains three widely separated sets of sequence related double zinc finger motifs of the CC/HH-type as well as a single CC/HH zinc finger. The Xenopus gene encodes a fourth double zinc finger and a single CC/HC zinc finger motif that have no counterpart in the fly protein. Alternative splicing of Xsal-1 transcripts gives rise to RNAs coding for either four, three or two double zinc fingers, respectively. The main expression domains of Xsal-1 in early development are confined to distinct regions along the lateral axon tracts within the midbrain, hindbrain, and spinal cord. Outside the central nervous system Xsal-1 is expressed in the facio-acoustic ganglion and in the developing limb buds. The pattern of expression suggests that Xsal-1 might be under control of signals emanating from the notochord and/or the floor plate and that it might function in neuronal cell specification.