Selective phosphodiesterases (PDEs) inhibitors have been widely studied as therapeutic agents for treatment of various human diseases, including cardiotonics, vasodilators, smooth muscle relaxants, antidepressants, antithrombotics, antiasthmatics, and agents for improving learning and memory. Although Sildenafil® and Vardenafil® have similar chemical formulae, the same target and interact with many of the same residues at the active site of phosphodiesterse-5 (PDE-5), they exhibit both in vitro and in vivo some important functional differences that could differentially affect behavior. Therefore we assessed whether repeated and chronic administration of Vardenafil and Sildenafil at a dose based upon human treatment can differentially affect aggressive, social, emotional and sexual behavior. To this aim, the effects of Sildenafil (10 mg/kg) or Vardenafil (2 mg/kg) (t.i.w., for 5 weeks) were observed in CD1 subordinate male mice in a low aggression and social subordination context. The results show that Sildenafil increased competitive aggression, environmental and social exploration, and reduced anxiety like behaviors as compared to controls, whereas Vardenafil had a significant major effect on appetitive and consummatory aspect of sexual behavior. This demonstrates that Sildenafil and Vardenafil, although being structurally and functionally similar, are characterized by different neuro-behavioral actions and can have differential therapeutic potentials.