After bleaching of visual pigment in vertebrate photoreceptors, all-trans retinal is reduced to all-trans retinol by retinol dehydrogenases (RDHs). We investigated this reaction in purified carp rods and cones, and we found that the reducing activity toward alltrans retinal in the outer segment (OS) of cones is >30 times higher than that of rods. The high activity of RDHs was attributed to high content of RDH8 in cones. In the inner segment (IS) in both rods and cones, RDH8L2 and RDH13 were found to be the major enzymes among RDH family proteins. We further found a previously undescribed and effective pathway to convert 11-cis retinol to 11-cis retinal in cones: this oxidative conversion did not require NADP ؉ and instead was coupled with reduction of all-trans retinal to all-trans retinol. The activity was >50 times effective than the oxidizing activity of RDHs that require NADP ؉ . These highly effective reactions of removal of all-trans retinal by RDH8 and production of 11-cis retinal by the coupling reaction are probably the underlying mechanisms that ensure effective visual pigment regeneration in cones that function under much brighter light conditions than rods.11-cis retinal ͉ 11-cis retinol ͉ all-trans retinal ͉ retinol dehydrogenase ͉ visual cycle L ight detection in vertebrates is mediated by rods and cones. Both rods and cones consist of two parts, the outer segment (OS) and the inner segment (IS). The OS contains the machinery responsible for conversion of a light signal to an electrical signal. The light-absorbing molecule, the visual pigment, is present in the OS and is composed of a chromophore, 11-cis retinal, and a protein moiety, opsin. Light isomerizes 11-cis retinal to all-trans retinal, which induces a conformational change in opsin to lead to activation of an enzymatic cascade to evoke a light response (1, 2).All-trans retinal, the product formed after light absorption, then dissociates from opsin and is reduced to all-trans retinol. This form of retinol is transported to the retinal pigment epithelium (RPE), isomerized, and oxidized to 11-cis retinal with multistep reactions. The newly synthesized 11-cis retinal is sent back to photoreceptors to regenerate visual pigment. This pathway of retinal processing (visual cycle) has been mainly studied in rods or rod-dominant retinas (3, 4). Because cones function under much brighter light conditions, the visual cycle for cones could differ from that for rods in a qualitative and/or quantitative way, as is seen in the phototransduction mechanism in rods and cones (5, 6).The reduction of all-trans retinal to all-trans retinol is attained by RDHs within a photoreceptor cell. This reduction could be the rate-limiting step of the visual cycle (7), and the rate of the reduction has been reported to be 10-40 times higher in cones than in rods under in vivo conditions (8). The supply of 11-cis retinal to regenerate visual pigment could be faster in cones. Several lines of evidence suggest that cone pigment is regenerated in an RPE-independent manner. Fo...