We studied epidermal autografts placed on four severely burned patients. All of the patients experienced skin fragility in the autograft sites, and three of the four patients reported spontaneous blisters. Epidermal-dermal adherence was objectively examined in one patient by comparing suction blistering times in the autograft and in a parallel, control, unburned site. Blisters formed in the autograft at 17 minutes, and the cleavage plane of the blister was below the lamina densa of the basement membrane. In contrast, the normal skin blistered at 65 minutes and had a superficial cleavage plane, above the basal lamina. In all four patients, the reconstituted basement membrane zone beneath the autografts was incomplete and lacked type IV (basement membrane) collagen 7-S sites and anchoring fibrils. We conclude that skin fragility, apparent as late as seven months after transplantation, may result from defective anchoring fibrils.