Epidermolysis bullosa (EB) was diagnosed in eight calves from four farms in the United Kingdom on the basis of clinical, histological and ultrastructural findings. In three affected herds, pedigree Simmental bulls had been mated with Simmental-cross cows. In a fourth herd two Holstein-Friesian calves were affected. Lesions included multifocal erosion and ulceration of the hard and soft palates, tongue, nares and gingiva, with onychomadesis (dysungulation). There was alopecia, erosion and crusting of the coronets, pasterns, fetlocks, carpi, hocks, flanks and axillae. Histopathological findings included segmental separation of full thickness epidermis from the dermis, with formation of large clefts containing eosinophilic fluid, extravasated red blood cells and small numbers of neutrophils. Follicular and interfollicular areas of skin were affected, with clefts extending around hair follicles and sometimes involving whole follicles. Ultrastructurally, there was evidence of vacuolar change within basal keratinocytes, corresponding to areas of histological clefting. Preliminary genetic screening of the candidate keratin genes (bKRT5 and bKRT14) has excluded mutations of these as the cause of this condition. Crown Copyright (C) 2009 Published by Elsevier Ltd. All rights reserved.