BACKGROUND: The correlation between histologically identified regeneration of retinal pigment epithelium (RPE) and functional outcome measured by multifocal electroretinography (mfERG) following surgical debridement is examined in a porcine model. In humans, visual acuity is reduced in diseases with RPE loss such as RPE tears and geographic atrophy. Hypopigmented RPE is known to cover the lesion after RPE debridement in the pig, but it is unclear whether this leads to a return of photoreceptor function. METHODS: RPE debridement was performed in ten pigs by vitrectomy and retinotomy, and by brushing the Bruch's membrane with a silicone catheter. Immediately following surgery (baseline) and after 2 and 6 weeks respectively, the animals were examined by mfERG, fundus photographs (FPs), fluorescein angiograms (FAs), and histopathology. RESULTS: The mfERG P1 amplitude was decreased 2 weeks (T2) after surgery; it returned to baseline 6 weeks (T6) after surgery. FPs, FAs, and histology showed partial repopulation of Bruch's membrane by hypopigmented RPE cells and atrophied outer segments at T2. At T6, normally pigmented RPE cells were identified, and the photoreceptor layer was restored. CONCLUSION: This is the first study to show that the histological regeneration of hypopigmented RPE correlates to a return of the retinal function, measured by mfERG.