Individuals who suffer extensive loss of skin, commonly in fires, are acutely ill, in danger of succumbing either to massive infection or to severe fluid loss. Patients who survive these early threats must often cope with problems of rehabilitation arising from deep, disfiguring scars and crippling contractures. In this report we describe the physiocochemical, biochemical, and mechanical considerations that form the basis for two-stage design of a membrane useful as an experimental wound closure. Stage 1 of the design, applicable to short-term acute use, calls for a membrane which displaces efficiently air pockets from a carefully prepared woundbed, free of weak boundary layers, and maintains the moisture flux through the wound at an optimal level. Optimization of the surface energy modulus of elasticity, energy to fracture and moisture permeability of the membrane are among the essential attributes of Stage 1 design. Stage 2 of the design, applicable to long-term, chronic use, focuses on a nonantigenic membrane which performs as a biodegradable template for synthesis of neodermal tissue. A survey of candidate materials suggests reasons for selection of a porous, crosslinked collagen—glycosaminoglycan coprecipitate as the chemical basis of an evolving design which was initiated 10 years ago. Over the past several years a set of membranes has been iteratively designed on this basis and has been used to cover satisfactorily large experimental fullthickness skin wounds in guinea pigs. Such membranes have effectively protected these wounds from infection and fluid loss for over 25 days without rejection and without requiring change or other invasive manipulation. When appropriately designed for the purpose, the membranes have also strongly retarded wound contraction and have become replaced by newly synthesized, stable connective tissue. Several rules relating the molecular structure and morphology of these membranes to cellular response of adjacent tissue have also been derived. This report is the first in a series which details the methodology of preparation and the record of performance.