The enzyme activities of normal-looking skin and blister fluid from a patient with recessive dystrophic epidermolysis bullosa (RDEB) were measured. Of the hydrolytic enzymes measured, both collagenase and neutral protease activities were considerably increased in the skin and blister fluid samples compared with values found in normal control skin and in blister fluid from a patient with a burn. In addition, skin from a healthy person cultured with RDEB blister fluid showed dermal-epidermal separation. These findings suggest that collagenase and neutral protease may be involved in the formation of blisters in RDEB.