The present study was carried out to evaluate the effect of a low-dose intravenous supplementation of L-arginine on insulin-mediated vasodilatation and insulin sensitivity. The study was performed in healthy subjects (n = 7) and patients with obesity (n = 9) and non-insulin-dependent diabetes mellitus (NIDDM) (n = 9). Insulin-mediated vasodilatation was measured by venous occlusion plethysmography during the insulin suppression test, evaluating insulin sensitivity. Experiments were performed twice in each subject in the presence or absence of a concomitant infusion of L-arginine (0.52 mg kg-1 min-1). L-Arginine restored the imparied insulin-mediated vasodilatation observed in obesity (22.4 +/- 4.1%, P < 0.01 vs. without L-arginine) and NIDDM (20.3 +/- 3.2%, P < 0.01 vs. without L-arginine). In healthy subjects, no effect on insulin mediated-vasodilatation was observed (24.8 +/- 3.1% vs. 21.4 +/- 3.1%). Insulin sensitivity was improved significantly (P < 0.001) in all three groups by infusion of L-arginine. No effect of L-arginine was observed on insulin, insulin-like growth factor I (IGF-I), free fatty acids (FFAs) or C-peptide levels during the insulin suppression test. Our data indicate that defective insulin-mediated vasodilatation in obesity and NIDDM can be normalized by intravenous L-arginine. Furthermore, L-arginine improves insulin sensitivity in obese patients and NIDDM patients as well as in healthy subjects, indicating a possible mechanism that is different from the restoration of insulin-mediated vasodilatation.