The organization of the Surfeit locus and the juxtaposition of at least five of the Surfeit genes (Surf-1 to -5) are conserved between mouse and human (Williams et al., 1988; Yon et al., 1993). In the mouse, the heterogeneous transcription start sites of the divergent Surf-1 and Surf-2 genes are separated by a maximum of only 73 bp (Williams and Fried, 1986). This region contains a bidirectional promoter composed of three major factor binding sites required for the efficient expression of both the Surf-1 and Surf-2 genes (Lennard and Fried, 1991). Here we report the isolation and characterization of the human Surf-1 and Surf-2 genes and their intergenic region. Although the major Surf-1 and Surf-2 transcription start sites are separated by 97 bp in the human and there are multiple differences in the mouse and human sequence between and around the transcriptional start sites, there is high conservation of the sequence specifying the three major factor binding sites of the bidirectional promoter. The three factor binding sites (HSu1, 2, and 3) present within the human promoter bind nuclear factors, of which the binding of HSu1 and HSu2 are competed by oligonucleotides carrying the corresponding mouse factor binding sites. The HSu3 site binds factors that are similar but apparently not direct homologs of those that bind to the equivalent mouse sequences. Human Surf-1 and Surf-2 cDNAs have been cloned and sequenced. The putative human Surf-1 and Surf-2 proteins are 77% and 69% identical to the corresponding mouse proteins.