The proposed research is directed toward a definition of the structure of the human visual pigments and toward an understanding of how these structures mediate human color vision. More specifically, we wish to test the model that the visual pigments in the three types of cones resemble the rhodospin of the rods in consisting of an apoprotein (opsin) covalently linked to the common 11-cis retinal chromophore, that differences in the absorption spectra among the visual pigments result from structural differences among the opsins, that those structural differences result from nucleotide sequence differences among the members of a multigene family encoding the opsins, and that the well known genetic variations in color vision result from mutations in those members that encode the cone opsins. To this end, we propose to clone, isolate and sequence the genes that encode the protein moieties of the human visual pigments fom both normal and mutant individuals. From these cloned genes we will produce the encoded proteins in appropriate host-vector systems, attach them to the 11-cis retinal and study the reconstituted visual pigments in vitro. This approach should allow a direct test of the model. Detailed analyses of many mutants should provide insights into the molecular structure and mechanism of action of the visual pigments that are important both to our basic understanding of vision and to its pathologic anomalies. Our strategy is (i) to isolate and characterize at the nucleotide level the gene encoding the best studied visual pigment, bovine rhodospin (ii) to use coding sequences from this gene as hybridization probes to isolate at least one of the human opsin genes ( e.g., that for human rhodopspin) from a library of genomic DNA clones, and (iii) to similarly use such a human gene isolate to identify and isolate other members of the postulated opsin multigene family in humans. The first step in this plan has been acccomplished.