Standardized through-and-through critical size defects were created in rat mandibles. After 12 weeks, the sites revealed a massive ingrowth of soft connective tissue, forming a transosseous core filling the defects. Upon reentry, the soft tissue inside the remaining bone defects was removed. On one side of the jaw, the defect was covered both buccally and lingually with an expanded polytetrafluoroethylene (e-PTFE) membrane, but on the other side no membrane was placed. Histologic analysis after 6 weeks revealed an essentially complete healing with bone of the membrane-covered defects. No cartilage was present in any of the specimens. At the control sites (no membrane), the amount of newly produced bone showed variations, most through defects revealing the presence of a remaining central portion of connective tissue. This investigation thus showed that predictable and successful bone regeneration can be achieved by the osteopromotive membrane method in treatment of nonunion defects filled with mature connective tissue.