Bilateral isometric handgrip (IHG) training lowers resting arterial blood pressure (BP) in medicated hypertensives. Numerous mechanisms have been suggested, but have yet to be investigated. One such mechanism is that of improved systemic endothelial-dependent vasodilation. The purpose of this investigation was twofold: (1) to determine if bilateral IHG training had any beneficial effects on endothelial-dependent vasodilation, and (2) to see if improved systemic endothelial-dependent vasodilation was responsible for lowering BP. Sixteen participants performed four, 2 min IHG contractions at 30% of their maximal voluntary effort, using either a bilateral (n = 7) or a unilateral IHG protocol (n = 9), three times per week for 8 weeks. Brachial artery (BA) flow-mediated dilation (FMD, an index of endothelial-dependent vasodilation, measured in both arms) was assessed pre- and post-training. Following bilateral IHG training, BA FMD improved in both arms (normalized to peak shear rate 0.005 +/- 0.001 to 0.02 +/- 0.002 s(-1), P