We assessed the prognosis of diabetic nephropathy during long-term antihypertensive treatment as compared to the prognosis during the natural history of this complication in a prospective study of all IDDM patients (N = 45) aged under 50 with onset of diabetes before the age of 31 who developed diabetic nephropathy between 1974 and 1978 at Steno Diabetes Center, and were followed until death or for at least 16 years [median 16 (4 to 21) years]. Antihypertensive treatment was started 3 (0 to 13) years after onset of diabetic nephropathy. Mean arterial blood pressure at start of antihypertensive treatment was 148/96 (sd 12/10) mm Hg and 143/86 (16/6) mm Hg during the whole interval of antihypertensive treatment (P < 0.01). The cumulative death rate was 45% (95% C.I. 38 to 52) 16 years after onset of diabetic nephropathy, in contrast to previous reports 88% and 94% 12 and 16 years after onset of diabetic nephropathy, respectively. The median survival time in our study exceeded 16 years as compared to five and seven years in untreated patients in the past. Uremia was the main cause of death (12 patients; 55%). In 1994 serum creatinine was 116 (74 to 311) mumol/liter in the 23 surviving patients. The preservation of kidney function and the prognosis of diabetic nephropathy has improved during the past two decades mainly because of effective antihypertensive treatment.