Thirty-eight patients with insulin dependent diabetes mellitus who had background retinopathy and no residual endogenous insulin secretion as assessed by plasma C-peptide determinations, were randomized to either conventional insulin treatment or to more intensive glucose control using ultralente insulin as basal cover and soluble insulin at mealtimes and were followed for five years. Plasma glucose profile and glycosylated hemoglobin were determined every eight weeks. Eye examinations were performed at the start of the study and after one, three and five years. Age, duration of diabetes, insulin dosage, glycemic control were comparable in the two groups. The mean plasma glucose profile was similar at entry in both groups and did not change in the conventionally-treated group. Mean plasma glucose profile 11.2 +/- 1 mmol/l with glycosylated hemoglobin level 10.7 +/- 0.3% fell to 7.9 +/- 0.4 mmol/l and 8.7 +/- 0.5% respectively during intensive treatment. Retinal morphology deteriorated during the follow-up with no significant differences between patients under unchanged conventional treatment and intensive insulin regimen. Proliferative retinopathy developed in six patients--three of these were under intensive insulin treatment. These data suggest that substantial long-term improvement of glycemic control does not affect progression of background retinopathy even when it is mild. The evolution of established retinopathy in insulin dependent diabetic patients is not only a function of poor glycemic control; other factors, either intrinsic or environmental, must also be important.