To evaluate the relationship between autonomic neuropathy (AN) and nephropathy we measured 24-h blood pressure (BP) and overnight urinary albumin excretion (UAE) in 38 patients with insulin dependent diabetes mellitus (IDDM). Autonomic function was evaluated by the heart rate response to deep breathing. Valsalva maneuver, heart rate at rest and BP variation with posture. Sympathetic cutaneous reflex was also tested in both inferior and superior limbs. Patients with mean day diastolic BP (DDBP) < or = 90 mmHg without AN (N = 15) compared to 12 normal controls had similar BP values, but compared to those with DDBP < or = 90 mmHg and AN (N = 12) they had lower night diastolic BP (NDBP) (66 +/- 4.8 vs 72 +/- 8.8 mmHg: p < 0.05) and UAE (9.8 +/- 2.3 vs 107.2 +/- 3.5 micrograms/min; p < 0.001). No difference in DDBP was observed between these two diabetic groups (80 +/- 3.9 vs 83 +/- 6.1 mmHg). Of the 11 patients with DDBP > 90 mmHg, only three were free of AN and only two of the eight with AN where free of diabetic nephropathy. The percentage day/night changes in systolic BP were lower in patients with AN (13 vs 7.9%; p < 0.05) and were inversely related to autonomic score, used as an index of the degree of autonomic dysfunction (r = -0.48; p < 0.01) and to UAE (r = -0.39; p < 0.05). Furthermore, UAE correlated with autonomic score (r = 0.69; p < 0.0001) and with NDBP (r = 0.44; p < 0.01). Our results show that AN in IDDM patients is associated with a reduced nocturnal fall in BP and suggest a pathogenic role of autonomic dysfunction in the development of diabetic nephropathy, possibly favoring both BP elevation during the night and increases in intraglomerular pressure.