Crx, an Otx-like homeobox gene, is expressed specifically in the photoreceptors of the retina and the pinealocytes of the pineal gland 1, 2. Crx has been proposed to have a role in the regulation of photoreceptor-specific genes in the eye and of pineal-specific genes in the pineal gland. Mutations in human CRX are associated with the retinal diseases, cone-rod dystrophy-2 (adCRD2; refs 3, 4, 5), retinitis pigmentosa 5 (RP) and Leber congenital amaurosis 5, 6 (LCA), which all lead to loss of vision. We generated mice carrying a targeted disruption of Crx. Crx–/–mice do not elaborate photoreceptor outer segments and lacked rod and cone activity as assayed by electroretinogram (ERG). Expression of several photoreceptor-and pineal-specific genes was reduced in Crx mutants. Circadian entrainment was also affected in Crx–/–mice.