TRANSMISSIBLE spongiform encephalopathies (TSEs) are a group of fatal neurodegenerative diseases in which an abnormal isoform of the cellular prion protein (PrPSc) accumulates in tissues of the central nervous system. Accumulation of PrPSc occurs in the retina, a rostral projection of the central nervous system, of both natural and nonnatural host species with TSEs (Foster and others 1999, Spraker and others 2002, Head and others 2003, 2005, Hamir and others 2004, 2005, Kercher and others 2004, Greenlee and others 2006, Hortells and others 2006). In retinas from scrapie-affected sheep, PrPSc accumulation is primarily observed in the inner and outer plexiform layers, and in the ganglion cell layer (Jeffrey and others 2001, Greenlee and others 2006). Recent studies have reported few (Hortells and others 2006) or no (Greenlee and others 2006) histological lesions in the retinas of sheep affected with scrapie. However, morphological changes in specific retinal cell types have been demonstrated (Smith and others 2008). Despite the morphological consequences of retinal PrPSc accumulation in sheep (Barnett and Palmer 1971, Smith and others 2008), the functional impact on the retina of these animals is unknown. In the current study, the effect of TSE on retinal function in a scrapie-infected Suffolk sheep using flash electroretinography was investigated.