In order to gain insight into the potential role of endothelin, a 21 amino acid peptide produced by endothelial cells, in the development of complications of diabetes mellitus, basal plasma endothelin levels were measured in 152 patients with diabetes mellitus (83 patients with type 1 diabetes mellitus, 69 patients with type 2 diabetes mellitus) and compared to those in 50 healthy controls. Blood was drawn at 8.00 a.m. under resting conditions and endothelin was determined after prior extraction by a sensitive radioimmunoassay. Endothelin levels were increased in patients with diabetes mellitus in comparison to controls (controls 0.9 +/- 0.1 pg/ml, type 1 diabetes mellitus 1.7 +/- 0.1, type-2-diabetes mellitus 2.0 +/- 0.1 pg/ml, p < 0.01 vs controls). 60% of patients with type 1 diabetes mellitus and elevated endothelin levels > 2.5 pg/ml (highest value measured in a control subject) had arterial hypertension with blood pressure > 140/90 mm Hg (p < 0.05 vs patients with normal endothelin levels). A reduced creatinine clearance (< 60 ml/min) was detected in 30% of patients with type 1 diabetes mellitus with elevated endothelin levels > 2.5 pg/ml, but only in 7% of patients with endothelin levels < 2.5 pg/ml (p < 0.05). In patients with type 1 diabetes mellitus and elevated endothelin levels diabetic retinopathy and peripheral neuropathy (p < 0.05) were more prevalent than in patients with normal endothelin values. 62% of patients with elevated endothelin levels had insufficient metabolic control (HbA1 concentrations above 10%). Positive correlations were found between endothelin and human atrial natriuretic peptide levels.(ABSTRACT TRUNCATED AT 250 WORDS)