Mild background retinopathy was studied prospectively during long-term strict blood glucose control in insulin-dependent diabetes mellitus. Forty-five subjects (21 women and 24 men with a mean age of 26.3 years and a mean duration of diabetes of 12.8 years) were randomly assigned to continuous subcutaneous insulin infusion, multiple injections, and conventional two-injection treatment. Eyes were examined two months before treatment, at the beginning of treatment, and after three, six, and 12 months. A progressive deterioration was found in the two-injection group during the study, but no significant changes were found in patients receiving multiple injections. A transient deterioration occurred after three months of continuous subcutaneous insulin infusion. Soft exudates appeared in 50% of the patients on the two intensified regimens, but no exudates were found in patients given conventional treatment. The morphologic changes seemed to be related to a large and rapid decrease in mean blood glucose or to an increased frequency of hypoglycemia, or both.