Dermo-epidermal separation in dystrophic epidermolysis bullosa (DEB) is thought to results from an abnormality of anchoring fibrils which, in normal skin, are stained selectively by the periodic acid-thiosemicarbazide-silver proteinate technique. This method was applied to non-lesional skin from four patients with generalized recessive DEB, five with localized recessive DEB and one with dominant DEB. No anchoring fibrils were present in the subjects with generalized recessive DEB, but they were morphologically normal in the case of dominant DEB and in three patients with mild localized recessive DEB. Two patients with a more severe form of localized recessive DEB possessed attenuated anchoring fibrils which lacked the normal banding of the mid-portion. The lamina densa, normally unlabelled, was consistently stained in patients with generalized recessive DEB, suggesting a biochemical abnormality of this structure.