The interaction with erythrocytes of four [VVO2L2]- complexes, with L = picolinate (pic), 5-cyanopicolinate (picCN), 3-aminopyrazine-2-carboxylate (przNH2), and 1,2-dimethyl-3-hydroxy-4(1 H)-pyridinonate (dhp), was studied. The thermodynamic stability at physiological pH is: [VVO2(dhp)2]- > [VVO2(przNH2)2]- > [VVO2(pic)2]- > [VVO2(picCN)2]-. With picCN and pic, V exists at physiological pH as H2VVO4-, with przNH2 as a mixture of H2VVO4- and [VVO2(przNH2)2]- and with dhp as [VVO2(dhp)2]-. In the systems with pic and picCN, H2VVO4- and the ligands cross the erythrocyte membrane independently, with dhp the uptake occurs by diffusion, whereas with przNH2 both the mechanisms are active. Inside erythrocytes stable VIVOL2 complexes are formed, indicating that there is no relationship with the stability and redox state of the administered compounds and that, if the metal ion changes its oxidation state in the cytosol as V does, unstable complexes in the extracellular medium could become stable inside the cells and contribute to the pharmacological action.