The progression of retinopathy was reevaluated at two years in 64 of the 68 patients with mild to moderate diabetic retinopathy, originally randomly assigned for an eight-month period either to intensified diabetic control with continuous subcutaneous insulin infusion (CSII) or to unchanged conventional injection treatment. Twenty-three of the 34 patients in the former group and 24 of the 34 in the latter agreed to continue to follow their original treatment assignment for a further 16 months. The others crossed over at the end of the first eight months of the study. During those first eight months, substantial lowering of blood glucose concentration had been achieved in the CSII group, unexpectedly associated with evidence of accelerated progression of retinopathy compared with the conventional injection treatment group. Glycemic separation was maintained at two years between the two groups continuing to receive the assigned treatment; during this time the mean retinopathy level deteriorated with conventional injection treatment and improved with CSII. At two years the degree of retinopathy in the two treatment groups was indistinguishable, with some trend to lesser overall deterioration with CSII. It is concluded that, in diabetics with mild to moderate nonproliferative retinopathy, the acceleration in activity associated with tightened control is not sustained and does not initiate vasoproliferative deterioration in retinopathy.