Forty-five diabetic patients were randomized and treated with continuous subcutaneous insulin infusion (CSII), multiple insulin injections (MI), or conventional insulin treatment (CIT) for 41 months. Near-normoglycemia was obtained with CSII and MI but not with CIT. A transient increase in microaneurysms and hemorrhages was seen at three months in CSII-treated patients. After 41 months, a moderate progression in microaneurysms and hemorrhages was registered, as assessed from fundus photographs, in all treatment groups. Fluorescein angiograms indicated a tendency (not statistically significant) to retarded progression of retinopathy in MI- and CSII-treated patients compared with CIT-treated patients. Soft exudates developed after three to six months of rapid tightening of metabolic control in 50% of patients on CSII and MI regimens. Those patients who had soft exudates had a slower progression of retinopathy three years later than those who did not develop soft exudates. Transient progression of retinopathy may be related to fluctuations in blood glucose levels, although a favorable effect of long-term improved metabolic control was not documented.