Clinical investigations are underway to determine the early natural history of senile macular degeneration. Drusen, and serous and hemorrhagic detachments of the retina and retinal pigmented epithelium, as well as choroidal neovascularization, are considered manifestations of senile macular degeneration and will be studied by serial recordings of the anatomical appearance and visual functioning of eyes at high risk of developing disease. These results will be compared with those obtained from fellow eyes with more advanced disease, as well as a matched group of normal eyes. Clinical chemical studies of serum levels of hormones such as cortisol, thyroid hormones, and of trace metal ions will also be conducted. The metabolism of trace metal ions will be explored further by quantitating the inexcretion in urine over a 24-hour period. By emphasizing investigations in affected family clusters, and using various genetic markers such as HLA antigens to segregate the affected from the nonaffected members of family clusters, it is hoped that those factors which are materially associated with the appearance and/or progression of various retinal degenerative conditions will be elucidated.