In insulin-dependent diabetic patients, nephropathy is a predictor of mortality and coronary heart disease. Impaired cardiac vagal function is an important factor in the pathophysiology of sudden cardiac death in coronary heart disease. Autonomic neuropathy in diabetes in particular involves vagal function. Bedside tests and 24-h measurements of cardiac parasympathetic activity were compared in 37 insulin-dependent diabetic patients, and the relationship between 24-h vagal activity and degree of nephropathy was investigated. Nephropathy was classified according to urinary albumin excretion as normoalbuminuria, incipient, and overt nephropathy. Mean age (approximately 30 yr) was not different among groups. The 24-h measurements of parasympathetic activity appeared more sensitive than bedside tests, as 33% of patients without cardiac autonomic neuropathy in bedside tests had 24-h vagal activity values below the 95% confidence limits of 14 healthy control subjects. Patients with incipient or overt nephropathy had significantly lower mean values for vagal activity during both wake and sleep time than healthy control subjects. Increasing degree of nephropathy was associated significantly with increasing attenuation of 24-h vagal activity (P less than 0.001). The covariation of degree of neuropathy and nephropathy may suggest common pathogenetic mechanisms. The reduced 24-h vagal activity, even in the early stages of nephropathy, could be an important risk factor for cardiac death in insulin-dependent diabetic patients.