The Diabetes Control and Complications Trial (DCCT) enrolled 1441 participants to address the role of intensive therapy for type 1 diabetes mellitus on the onset and progression of microvascular complications. To examine the timing of elevated systolic BP (SBP) and diastolic BP (DBP) and increased albumin excretion rate (AER) in the progression to clinical diabetic nephropathy (AER > 300 mg/24 h on two consecutive visits from a baseline of <100 mg/24 h) and, importantly, to control for initial values of hemoglobin A(1c), a retrospective case-control study was assembled from the records of the publicly released DCCT data. Participants who progressed to clinical diabetic nephropathy-progressors-were matched with participants of the same gender and treatment group who had similar baseline values for DBP, SBP, AER AER and hemoglobin A(1c), but who did not progress to clinical diabetic nephropathy-matched controls. In the conventional treatment group, the 21 progressors exhibited a significant rise in mean AER (above their own baseline levels and above values in the matched controls) at year 2 of the DCCT. In contrast, the progressors' mean DBP and SBP were not significantly higher than baseline until year 3 (DBP) or year 4 (SBP) and not significantly higher than the matched controls until year 4 (both DBP and SBP). On the individual level, 19 of 21 (90%) progressors reached clinical diabetic nephropathy before the diagnosis of hypertension (140/90 mmHg). In the intensive treatment group, however, the rise in DBP preceded the rise in AER by 1 to 2 yr among the six progressors. Both intensively treated progressors who experienced hypertension reached this before AER > 300 mg/24 h. These results underline the early and prognostic rise in AER in diabetic patients, but only in those who received conventional treatment. The evolution of diabetic renal disease may follow a different course in patients who receive intensive diabetic treatment.