Intensive glycemic control (IGC) in previously hyperglycemic insulin-dependent diabetes mellitus (IDDM) patients is associated with a decreased long-term risk of progression of diabetic retinopathy (DR); up to 12 months after institution of IGC, however, the risk of progression of DR transiently increases. In an observational study, a cohort of 122 patients with IDDM was followed prospectively for changes in glycosylated hemoglobin (HbA1, normal < 8%) and in DR 0-12 months after institution of IGC. In six of these patients (women, mean age 24 years, duration of diabetes 14.3 years, with incipient nephropathy and retinopathy) a total of seven eyes went blind after 6-12 months of IGC, despite laser coagulation treatment. From the whole sample, a control groups of eight patients (six women) was set up, matched for age, duration of IDDM, degree of retinopathy, visual acuity, blood pressure, and microalbuminuria, with preserved vision after 12 months of IGC. In the case patients, the mean (95% confidence interval) initial HbA1 was 14.9% (13.8%-16.1%), versus 13.4% (12.4%-14.4%) in the control patients (p < 0.05). The mean HbA1 decrements after 4 months of IGC, were 3.0% (1.9%-4.1%) in the cases, and 2.1% (1.2%-3.0%) in the controls (NS); and after 12 months, the respective decrements were 4.9% (2.4%-7.4%) in the cases versus 2.0% (0.5%-3.5%) in the controls (p = 0.04). In conclusion, IGC with a decrement of > 2% per year is associated with a high risk of progression of antecedent diabetic retinopathy to blindness in IDDM patients with an extremely high initial HbA1.(ABSTRACT TRUNCATED AT 250 WORDS)