The sensitivity of the mouse anococcygeus to contraction by oxytocin was shown to be Mg2+-dependent. Decreasing [Mg2+]0 from the optimal concentration of 1 to 0 mM caused a 20-fold parallel rightward displacement of the oxytocin dose-response curve. Contractions to oxytocin-related peptides (Arg-vasotocin, Arg-vasopressin and Lys-vasopressin) were also Mg2+-dependent, but those to other drugs (carbachol, methoxamine and thyrotrophin releasing hormone) were not. The onset of the potentiating effect of Mg2+ was rapid, full potentiation occurring within 70 s. 1-Deaminopenicillamine 8-ornithine-vasotocin produced competitive antagonism of responses to oxytocin, but was more potent in the absence (pA2 = 8.01) than in the presence of Mg2+ (1 mM; pA2 = 7.52). Thus, physiological concentrations of [Mg2+]0 enhanced oxytocin agonist potency but decreased oxytocin antagonist potency; possible mechanisms are discussed.