This study was designed to investigate potential factors involved in the disruption of the circadian blood pressure (BP) pattern in diabetes mellitus, as well as the relation between BP, cardiac autonomic neuropathy, and estimated cardiovascular risk. We studied 101 diabetic patients (58% with type 2 diabetes; 59% men), age 21-65 yrs, evaluated by 48 h BP monitoring. We performed three autonomic tests in a single session: deep breathing, Valsalva maneuver, and standing up from a seated position. Patients were classified according to the number of abnormal tests and their 10 yr risk of coronary heart disease or stroke. The prevalence of non-dipping 24 h patterning ranged from 47.6% in type 1 to 42.4% in type 2 diabetes. The awake/asleep ratio of systolic BP (SBP) was comparable between patients with or without abnormal autonomic tests. Pulse pressure (PP) was significantly higher in patients with > or =1 abnormal autonomic test (p < 0.001). Ambulatory SBP was significantly elevated in the group with higher risk of coronary heart disease (p < 0.001). Patients with higher stroke-risk had higher SBP but lower diastolic BP, and thus an elevated ambulatory PP by 9 mmHg, compared to those with lower risk (p < 0.001). Cardiac autonomic neuropathy is not the main causal-factor for the non-dipper BP pattern in diabetes mellitus. The most significant finding from this study is the high ambulatory PP found in patients with either cardiac autonomic dysfunction or high risk for coronary heart disease or stroke. After correcting for age, this elevated PP level emerged as the main cardiovascular risk factor in diabetes mellitus.