Best's vitelliform macular degeneration is caused by mutations in the VMD2 gene and characterised by a loss of the light-peak amplitude in the EOG. Since the light-peak arises from activation of basolateral Cl channels in the retinal pigment epithelium (RPE) and since the VMD2 gene product, bestrophin-1, was described as Ca²⁺-dependent Cl channel it is believed that the these symptoms are due to loss in Cl channel function. To test this hypothesis we investigated bestrophin-1 deficient mice. These mice do not show a retinal degeneration and normal light-peak amplitudes. In patch-clamp recordings, freshly isolated RPE cells from vmd2 -/- mice showed mild inwardly rectifying whole-cell Cl currents which could be stimulated by increasing intracellular free Ca²⁺ from 10 nM to 400 nM from 8.0 ± 2.1 pA/pF (n = 2) to 24.8 ± 10 pA/pF (n = 6). With these characteristics the Cl currents were indistinguishable from those of wild-type mice: currents with the same voltage-dependence and Ca²⁺-dependent activation: at 10 nM 11 ± 2.1 pA/pF (n = 6) and at 400 nM 26.9 ± 4.9 pA/pF (n = 22). We conclude that loss of bestrophin-1 Cl channel function did neither change the light-peak, membrane currents nor lead to retinal degeneration, possibly due to compensation by other Cl channels. Thus Best's disease might be caused by alterations of other bestrophin-1 associated functions.