Neurofibromas contain approximately 30-50% collagen of their lipid-free dry weight, which is about half of the value of skin but approximately twice that described for peripheral nerve endoneurium. Immunohistochemical stainings indicate that neurofibromas contain types I, III, IV, and V collagens and fibronectin. Most of the neurofibroma cells are type IV collagen and S-100 protein positive, which provides immunohistochemical evidence that neurofibromas are mostly composed of Schwann cell-like cells. The proteoglycan/collagen ratio is 4 to 10 times higher in the neurofibromas than in the surrounding dermal tissue. This would explain the typical soft consistency of the neurofibromas and may contribute to a favorable milieu for tumor growth. Pure fibroblastic cell cultures are obtained from neurofibromas after repeated passages. The cultured cells synthesized type I and III collagens and fibronectin, indicating that these cells are important in the production of the fibrous connective tissue proteins in neurofibromas.