cDNA clones of the human c-fes mRNA were isolated. Nucleotide analysis showed that c-fes mRNA contains a 2514 nucleotide open reading frame, which could encode for a 93 kDa protein, and both 5' and 3' v-fes nonhomologous sequences. Primer extension experiments confirmed that the longest isolated cDNAs are about the same length as the entire human c-fes mRNA. Sequence comparison between human c-fes cDNA and the corresponding genomic regions identified a 5' viral-non homologous exon (exon 1) located 491 bp upstream from the first v-fes homologous exon. The genomic region surrounding c-fes exon 1 contains a CpG island and acts as a promoter in vitro. Analysis of the 5' end of mouse c-fes cDNA suggested that the 5' human and mouse gene structure are similar.