1. A clinical, radiological and histological description of a patient with fibrogenesis imperfecta ossium is given. We think that this is the first case in which diagnosis has been made during the life of the patient.

2. The disease is characterised by a defect in the formation of the collagen fibres of the bone matrix. There is also a failure of normal calcification of the matrix, giving rise to the appearance of wide "osteoid" seams. When examined with the polarising microscope and when stained with Gomori's reticulin stain the collagen fibres can be seen to be grossly deficient and abnormal.

3. The patient presented at the age of fifty-four years with bone pain and multiple fractures. The only biochemical abnormality detected in the plasma was an elevated alkaline phosphatase. He was also in negative calcium balance.

4. Treatment with vitamin D₂, later changed to dihydrotachysterol, appears to have produced clinical, biochemical and radiological improvement. It appears that a direct action of the vitamin on the abnormal bone collagen must be postulated, in addition to its known actions on the calcifying mechanisms.

5. An unusual feature of the case was the slow development of a total unresponsiveness to large doses of vitamin D₂, in spite of a markedly elevated level of vitamin D in the plasma. There was later a response to a much smaller dose of dihydrotachysterol, which is being maintained to date.

A case is reported of a woman in whom the bones of one upper limb have been progressively disappearing during at least eleven years. Investigations have thrown no light on etiology or treatment.

1. A description is given of the pathology of a generalised skeletal disease characterised by a defect in the formation of the collagen fibres of the bone matrix—"fibrogenesis imperfecta ossium."

2. Material from two cases, a woman of fifty-six and a man of sixty-four, was examined. All the samples of bone from both patients showed the same defect, which was severe in most of the specimens, and there was radiographic evidence of similar widespread bone changes in both cases.

3. The defect is clear-cut and striking histologically, provided that sections are examined with a polarising microscope, and/or by reticulin methods.

4. As a result of the defect in the bone matrix this fails to calcify, or calcifies imperfectly, showing wide osteoid borders as in severe osteomalacia. But the fibre defect separates it quite clearly from osteomalacia, in which the fibre structure of the osteoid tissue is normal. Moreover neither the biochemical findings (Case 2) nor the radiographic appearances correspond with those of osteomalacia.

5. The collagen fibre defect is confined to the bone matrix; no defect was found in the soft tissue collagen, and even the periosteum shows a normal fibre structure.

6. Both the clinical and the histological evidence indicate that the disease is not congenital, but was, in these two patients, apparently acquired during middle age. There was no family history of bone disease.

7. The cause of the condition is quite obscure. It is not inflammatory or neoplastic, nor is there histological or clinical evidence of a toxic origin. If it is a deficiency disease it is unlike any known vitamin or other chemical deficiency.