The eye needs to biosynthesize 11-cis-retinoids because the chromophore of rhodopsin is 11-cis-retinal. The critical metabolic step is the endergonic isomerization of free all-trans-retinol (vitamin A) into 11-cis-retinol. This isomerization process can take place in isolated membranes from the retinal pigment epithelium in the absence of added energy sources. Specific binding proteins probably do not serve as an energy source, and since all of the reactions in the visual cycle are shown here to be reversible, trapping reactions also do not participate in the isomerization reaction. One previously unexplored possibility is that the chemical energy in the bonds of the membrane itself may drive the isomerization reaction. A group transfer reaction is proposed that forms a retinyl ester from a lipid acyl donor and vitamin A. This transfer can drive the isomerization reaction because the all-trans-retinyl ester is isomerized directly to 11-cis-retinol. Thus, the free energy of hydrolysis of the ester is coupled to the thermodynamically uphill trans to cis isomerization. The prediction of an obligate C-O bond cleavage in the vitamin A moiety during isomerization is borne out. Although the natural substrate for isomerization is not known, all-trans-retinyl palmitate is processed in vitro to 11-cis-retinol by pigment epithelial membranes.