The purpose of this research is to investigate metabolic factors which are associated with the development of cataracts in humans. It is postulated that their identification may lead to methods which either prevent cataract formation or halt their progression. In a controlled age paired study of diabetics and nondiabetics we found a similar prevalence of lens opacities in both groups. However, the patients with diabetes mellitus appeared to be at greater risk of developing visually significant cataracts. A higher incidence of cataracts was found among diabetics who were treated with oral hypoglycemic agents than among diabetics who were treated with either insulin or diet alone. Studies of patients who had received corticosteroid therapy showed that they are more likely to have cataracts than either the diabetic or untreated nondiabetic population. A prospective study of this finding has been initiated with observation before treatment with corticosteroids, at intervals after treatment and at various dosages for different durations of exposure. Studies in animals suggesting an association between riboflavin deficiency and cataract formation has prompted us to undertake similar studies in humans. To date, we have failed to show a correlation between riboflavin levels in humans and cataract formation. Our studies showing a markedly higher prevalence in humans who have decreased levels of galactosemic enzymes and who are presumably heterozygous carriers of galactosemis are being continued to determine if modification of their diet by exclusion of their diet will halt the progression of their cataract. In this latter group of patients family studies are being performed both to prove the existence of the inherited trait and in hopes of preventing cataracts in identified heterozygotes.