Serum total and high-density lipoprotein (HDL) cholesterol were measured in a sample of individuals examined between 1984 and 1986 for the Wisconsin Epidemiologic Study of Diabetic Retinopathy. There was a significant trend for increasing severity of diabetic retinopathy and of retinal hard exudate with increasing cholesterol in insulin-using persons. Cholesterol levels were not related to the severity of either ocular condition in older-onset patients. High-density lipoprotein-cholesterol was unrelated to the severity of either lesion. In multiple logistic regression analyses, cholesterol was not a significant factor in describing the severity of retinopathy in any group but was a significant factor in describing the severity of retinal hard exudate. Glycosylated hemoglobin and diastolic blood pressure were significant descriptors of the severity of retinopathy in younger-onset patients in these multivariate analyses. Diastolic blood pressure added significantly to explaining the severity of hard exudate in older-onset insulin users. These data support the current management strategies for diabetes, which include control of level of glycemia, blood pressure, and blood lipids.