Despite the presence of this virgin opsin, Rpe65-/- rods are behaving like dark-adapted rods. These results argue that opsin which has not been exposed to 11-cis retinal and is constitutively phosphorylated, does not generate the activity generally associated with the bleached apoprotein. However, increased light-independent activation of transducin (due to bleached opsin) could be demonstrated after the addition of exogenous 11-cis retinal. We hypothesize that free opsin in the Rpe65-/- rods does not cause degeneration of rods by constitutive activation of the phototransduction cascade; but rather rods may die due to other causes such as the impairment of RPE function due to excess unprocessed retinyl-esters in the RPE.