The diagnostic survey of these two patients revealed periapical infections and a bacterial hypersensitivity which might have accounted for the repeated attacks of nongranulomatous uveitis. In addition, however, both had evidences of a disturbance in the systemic fat metabolism with a marked elevation of the total plasma lipids, especially involving the total cholesterol. These observations suggested that the stimulus of the repeated uveal inflammation in these two patients with a concomitant hypercholesteraemia might have initiated the deposition of lipids in the retina and subretinal space.In the exploration of this idea, the somewhat confused literature on Coats's disease was first reviewed and analysed, especially for any information relative to lipid deposition in the eye or disturbance in the fat metabolism. Thereafter, all cases in the clinical and eye pathology files of the Wilmer Institute, in which a positive or suggested diagnosis of Coats's disease had been made, were sought for and restudied. As far as was possible, all patients in whom a final clinical or histological diagnosis of Coats's disease was justified, were recalled for further examination and determination of their blood lipids. The histological material from those patients in whom the histopathological diagnosis had been made, was restained and studied for the deposition and possible identification of any lipids in the retina and subretinal space. Finally, certain experiments were undertaken, exploring the possibility that a repeated or prolonged inflammatory insult might result in the deposition of lipids in the retina or subretinal space. * This paper is divided into three parts. The first two were prepared by Dr. Alan C. Woods and Dr. James R. Duke. The experimental work for Part III was done by these two authors and the data were collected prior to the death of Alan Woods and a rough manuscript drawn up. A week before he died in Johns Hopkins Hospital, Woods told his more junior colleague that unfortunately the latter would have to complete the final manuscript alone.