1. The major collagen fraction of skin, which in vivo consists of tropocollagen molecules aggregated into extracellular fibres, has been extracted from forty-nine normal subjects and nineteen patients with inherited and acquired disorders of connective tissue.
2. In normal subjects the chemical stability of this fraction progressively increased up to the age of 60.
3. This fraction was less stable than normal in patients with homocystinuria, Werner's syndrome, myositis ossificans progressiva, pseudoxanthoma elasticum, juvenile osteoporosis and acromegaly.
4. In osteogenesis imperfecta (OI) the stability of this fraction was normal in those patients with markedly blue sclerae, although the amount which could be extracted from the skin was low: opposite results were found in those OI patients with sclerae of normal colour.
5. This study provides preliminary evidence of collagen abnormality in several heritable disorders of connective tissue.