Ten rhodopsin mutations have been found in a screen of 282 subjects with retinitis pigmentosa (RP), 76 subjects with Leber congenital amaurosis, and 3 subjects with congenital stationary night blindness. Eight of these mutations (gly 51-to-ala, val 104-to-ile, gly 106-to-arg, arg 135-to-gly, cys 140-to-ser, gly 188-to-glu, val 209-to-met, and his 211-to-arg) produce amino acid substitutions, one (gln 64-to-ter) introduces a stop codon, and one changes a guanosine in the intron 4 consensus splice donor sequence to thymidine. Cosegregation of RP with gln 64-to-ter, gly 106-to-arg, arg 135-to-gly, cys 140-to-ser, gly 188-to-glu, his 211-to-arg, and the splice site guanosine-to-thymidine indicates that these mutations are likely to cause retinal disease. Val 104-to-ile does not cosegregate and is therefore unlikely to be related to retinal disease. The relevance of gly 51-to-ala and val 209-to-met remains to be determined. The finding of gln 64-to-ter in a family with autosomal dominant RP is in contrast to a recent report of a recessive disease phenotype associated with the rhodopsin mutation glu 249-to-ter. In the present screen, all of the mutations that cosegregate with retinal disease were found among patients with RP. The mutations described here bring to 35 the total number of amino acid substitutions identified thus far in rhodopsin that are associated with RP. The distribution of the substitutions along the polypeptide chain is significantly nonrandom: 63% of the substitutions involve those 19% of amino acids that are identical among vertebrate visual pigments sequenced to date.