Phototransduction in vertebrate rod and cone photoreceptor cells involves G protein-mediated light stimulation of cGMP hydrolysis. Enzymes of the cGMP hydrolysis cascades of rods and cones are products of different genes. Three different classes of cones in the human retina are maximally sensitive to either blue, green, or red light. Distinct opsin genes are expressed in each type of cone. The distribution of cone types in human retina was determined using anti-peptide antibodies that recognize specific amino acid sequences in green/red opsin and blue opsin. These antibodies together with an anti-peptide antibody against T cα were used in double labeling experiments to demonstrate the presence of the T cα peptide in all types of cones. cDNA clones corresponding to human rod and cone transducin α subunit (T cα and T cα) genes were isolated. Southern blot analyses of human genomic DNA suggest that there is only one rod T α gene but more than one cone T α gene. The multiple T cα genes could be closely related genes or different T cα alleles, or one could be a pseudogene.