We have previously shown that there is a temporal difference in human CRX: gene expression compared with that of mouse Crx. We have now characterized these genes at the genomic and transcriptional levels and here we expand on this earlier report. Human CRX: spans 25 kb and has six exons, and mouse Crx: spans 15 kb and has four exons. We isolated seven human and two mouse mRNAs generated by alternative splicing of a variable 5′ untranslated region. The human and mouse genes share an evolutionarily conserved promoter, which contains OTX/CRX type and SP1/AP2 binding sites and drives expression of two conserved transcripts in both species. Additionally, the human gene has a second human-specific promoter, which has OTX/CRX type binding sites and drives expression of five other transcripts. Band shift assays have shown that six of the seven candidate OTX/CRX elements bind CRX in vitro, possibly implying that the gene can regulate its own expression. These data may account for the differences in temporal expression in vivo: we have previously reported between these two species.