Viscum album leaf extract (VA) has a folk reputation as an antihypertensive agent in Nigeria. Evidence suggests that it has a vasorelaxant effect that is endothelium dependent involving the release of nitric oxide (Ekpenyong et al, 1999). However, VA showed a relaxant effect in endothelium-denuded preparations (Ekpenyong et al, 1999) suggesting that it might also act on the vascular smooth muscle via calcium-dependent mechanisms. The present study was designed to investigate this possibility. Fresh leaves of Viscum album were harvested and ground into powder. An aqueous extract was prepared and phytochemical analyses done. Sprague-Dawley rats (n=6) were anaesthetized using a 25% urethane and 1% chloralose mixture given intraperitoneally at a dose of 5ml/kg. Thoracic aortae were obtained and cut into 2 mm ring segments in Physiological salt solution (PSS; composition (mmol.l^-1): NaCl, 119; KCl, 4.7; KH₂PO₄ , 1.2; MgSO₄, 1.2; NaHCO₃, 14.9; CaCl₂, 1.6; glucose, 11.5). Each aortic ring was mounted in a tissue bath containing PSS and continuously bubbled with a 95% O₂-5% CO₂ gas mixture at a temperature and pH of 37°C and 7.4 respectively (Adegunloye and Sofola, 1997). Relaxation response studies to VA (2-16 mg.ml^-1) were done following pre contraction with 10^-7 mol.l^-1 noradrenalin or 60mmol.l^-1 KCl. The IC₅₀ of VA in noradrenalin pre-contracted rings was 5.2 ± 0.79mg.ml^-1 while the IC₂₅ in KCl pre-contracted rings was 7.1±0.56 mg.ml^-1. These concentrations of V. album were used in subsequent experiments. Concentration response curves (CRCs) to noradrenalin (10^-9 to 10^-5mol.l^-1), KCl (10-80mmol.l^-1) and CaCl₂ ((2.5 x 10^-4 to 1.6 x 10^-1 mol.l^-1) were constructed with and without VA. Phasic contraction to 10^-5 mol.l^-1 noradrenalin was carried out in Ca-free EGTA (N′N′-ethylene glycol tetra acetic acid) PSS (Perry & Webb, 1991). The results are presented as mean ± SEM. The student’s t test for paired data was used for statistical analysis. P<0.05 was taken as statistically significant. Phytochemical analyses showed the presence of flavonoids and tannins. The CRCs to noradrenalin or KCl were significantly (P<0.05) attenuated and shifted to the right in the presence of the VA. Also the CRC to CaCl₂ in the presence of noradrenalin or KCl was attenuated and shifted to the right by VA, while the phasic response to noradrenalin was diminished (P<0.05). These results suggest that the vasorelaxant effect of VA may be mediated by a non-specific non-competitive inhibition of Ca²⁺ influx as well as inhibition of Ca²⁺ mobilization from intracellular stores. These calcium antagonistic effects may be due its flavonoid or tannin content.