In response to light, the mouse retinal pigment epithelium (RPE) generates a series of slow changes in potential that are referred to as the c-wave, fast oscillation (FO) and light peak (LP) of the electroretinogram (ERG). While the FO is known to reflect a Cl− conductance generated at the basal membrane of the RPE, the specific channel (s) underlying this potential has not been identified. In the present study we examined two strains of mice with cftr mutations to define the contribution that cystic fibrosis transmembrane regulator (CFTR)-mediated Cl− conductance makes to the mouse ERG. Responses obtained from cftrΔ508/Δ508 mice exhibited an overall reduction in all components generated by the RPE in response to light without alteration of the luminance response function. Responses obtained from cftr−/− mice were also reduced in amplitude. These results illustrate the usefulness of ERG analysis of mice deficient in ion channels that are expressed in the RPE, and indicate that CFTR contributes to the generation of RPE-driven ERG components, but that it is not the sole generator of any one of these components.