It has been reported that Ca²⁺ currents in isolated human vas deferens smooth muscle cells exhibit components that are differentially sensitive to Ni²⁺ (T-type current) and verapamil (L-type current). Thus, Park et al., (2004) suggested that T-and L-type VOCs contribute to the tissue contractility. This study investigated the effects of T-type Ca²⁺-antagonists, mibefradil and flunarizine compared to nifedipine, a prototype L-type Ca²⁺ antagonist. Given that mibefradil and flunarizine also block L-type VOCs, their potencies in this tissue as L-type Ca²⁺ antagonists were determined. Human vas deferens specimens obtained after elective vasectomies (with consent of patients and College Ethical approval) were cut into strips of longitudinal muscle or rings of circular muscle. These were set up for tension recording and superfused with Krebs medium (36°C). Contractions were evoked by noradrenaline (NA) in the presence of Ca²⁺ antagonists and expressed as a percentage of drug-free controls (mean ± S.E.M). Statistical analysis was by one-way ANOVA followed by a priori t-test using within-groups variance from ANOVA. Differences between time-matched controls and drug groups were considered significant at P < 0.05. NA (0.1-100 µM) evoked rhythmic and tonic contractions, which were inhibited by nifedipine (0.01-0.1 µM) or by mibefradil (1-10 µM) such that contractions to NA (100 µM) in longitudinal and circular muscles were reduced respectively by 88.4 ± 1.3%, (n=9) and 87.03 ± 2.7%, (n=8) in nifedipine (0.1 µM); by 89.1 ± 3.4%, (n=5) and 68.5 ± 3.8%, (n=7; P< 0.05) in mibefradil (10 µM) and modestly by 18.3 ± 6.3% (n=6) and 27.0 ± 10.8% (n=5) in flunarizine (10 µM). The drugs’ potencies as antagonists of L-type VOCs were determined against contractions to high K⁺ (120 mM, in the presence of FPL 64176, 1 µM). The contractions in longitudinal and circular muscle had different times to peak and decline but were inhibited comparably by nifedipine (IC₅₀ longitudinal and circular muscle, ~2 nM) or by mibefradil (IC₅₀ longitudinal muscle, 1.1 µM; circular muscle, 2.4 µM) and were insensitive to flunarizine (up to 30 µM). These results suggest that the effects of mibefradil and flunarizine, at concentrations found to be effective against noradrenaline-induced contractions of human vas deferens involve the blockade of L-type VOCs. The difference in the effect of mibefradil in longitudinal and circular muscle may involve factors that modulate the activation and/or sensitivity of L-type VOCs to the drug. Overall, the results indicate that noradrenaline-induced contractions of human vas deferens depend primarily on nifedipine-sensitive L-type VOCs than on mibefradil or flunarizine-sensitive T-type VOCs.