Exposure to lead is known to cause vasoconstriction, exact mechanism of which remains to be elucidated. In this study, we investigate contractile responses of rat aortal rings equilibrated with Pb(II) in organ bath system, explore pathways responsible for hypercontraction and examine two ameliorators of lead-induced hypercontraction. At 1 μmol L(-1) Pb(II), aortal rings showed an average increase of 50% in isometric contraction. Incubation of rings, unexposed to Pb(II), with 1 μmol L(-1) sodium nitroprusside (nitric oxide (NO) donor), 100 μmol L(-1) apocynin (reactive oxygen species (ROS) inhibitor), and 100 μmol L(-1) indomethacin (cyclooxygenase inhibitor) lead to decrease in phenylephrine-induced contraction by 31, 27, and 29%, respectively. This decrease of contraction for Pb(II)-exposed rings was 48, 53, and 38%, respectively, indicating that ROS- and NO-dependent components of contractions are significantly elevated in Pb(II)-induced hypercontraction. Cyclooxygenase-dependent contractile component did not show significant elevation. Eugenol and carvacrol are plant-derived phenols known to possess antioxidant activity and hence could act as possible ameliorators of hypercontraction. At saturating concentrations of 100 μmol L(-1), eugenol and carvacrol caused a decrease in contraction by 38 and 42% in unexposed rings and 46 and 50% in Pb(II)-exposed rings. Co-incubation of rings with eugenol/carvacrol and various inhibitors suggests that both these active principles exert their relaxant effect via quenching of ROS and stimulation of NO synthesis. To conclude, Pb(II) is shown to induce hypercontraction of aortal rings through elevation of ROS and depletion of NO. This hypercontraction is effectively mitigated by eugenol and carvacrol.