L-Arginine, the natural precursor of NO, is infused in patients to restore endothelial function. Concentrations up to 7.5 mM L-arginine have been measured after parenteral administration. We investigated whether such high concentrations of amino acids influence blood viscosity in vitro, Incubation of whole blood from healthy volunteers with L-arginine, D-arginine, which has no effect on stereospecific NO synthases (NOS), the NOS substrate L-AME, the NOS inhibitor L-MNA, the amino acids L-lysine and L-glutamic acid, and finally NaCl dose-dependently decreased (up to 30% at 10(-2) M) low shear viscosity, which is primarily determined by erythrocyte aggregation. In contrast, the lipophilic NOS inhibitor L-NAME had no effect on low shear viscosity. All molecules failed to influence high shear viscosity, which is primarily determined by red cell deformability, and the erythrocyte shape remained unaltered. We conclude that high concentrations amino acids may decrease blood viscosity at low shear rate independent of NOS activity. This effect may contribute to the improved blood dow after intravascular administration of L-arginine.