The role of sulfhydryl and disulfide groups as determinants of rabbit mesenteric arterial responses to various contractile agonists were determined. The addition of 1×10^-3 M or of 1×10^-2 M 2-mercaptoethanol (2-M Et), a sulfhydryl reagent, produced a leftward displacement (potentiation) of the concentration-response curves of mesenteric arterial strips for KCl. Dithiothreitol (DTT), a reagent that reduces disulfide bonds to sulfhydryl groups, also potentiated the contractile response to KCl in this strip. In mesenteric arterial strips treated with 14 mM KCl after exposure to Ca²⁺-free Krebs' bicarbonate solutions containing 0.1 mM EGTA, the addition of CaCl₂ in a concentration of 2.5 mM caused a contraction (14 mM KCl-induced Ca²⁺-contraction). The presence of 2-MEt or DTT expectedly potentiated this 14 mM KCI-induced Ca²⁺-contraction. Verapamil, a calcium antagonist, inhibited the 14 mM KCI-induced Ca²⁺-contraction both in the presence and the absence of these sulfhydryl reagents. 2-MEt also potentiated the contractile responses of mesenteric arterial strips to histamine, norepinephrine, angiotensin II and prostaglandin F_2α suggesting that the potentiation by the sulfhydryl reagent is a nonspecific effect. This sulfhydryl reagent potentiated the each agonist-induced Ca²⁺-contraction. It is concluded that reduction of a disulfide bridge to a sulfhydryl group at Ca²⁺-channels increases transmembrane influx of Ca²⁺ in strips of rabbit mesenteric artery and the increased Ca²⁺ influx in turn accompanied the contractile responses to various agonists.