Since adenosine is a vascular tone modulator, we examined the effect of adenosine and congeners in the vascular reactivity of isolated human placental vessels and in perfused cotyledons. We characterized its vasomotor action and tentatively identified the receptor subtypes and their intracellular signalling mechanisms. We recorded isometric tension from the circular layer of chorionic vessel rings maintained under 1.5 g basal tension or pre-contracted with KCl. The relative order of potency of adenosine and structural analogs is consistent with the expression of A_2B receptors; NECA (5'-N-ethylcarboxamideadenosine) being the most potent. The maximal contraction ranged from 45-60% of the KCl standard response, except for an A_2A receptor agonist that did not exceed 15%. Consistently, NECA was 100-fold more potent than adenosine to raise the perfusion pressure of ex-vivo perfused cotyledons. In contrast, a selective A₃ receptor agonist relaxed pre-contracted rings of chorionic vessels. While a selective A₃ receptor antagonist was ineffective to antagonize the adenosine-induced contraction, A₂ or A₁ receptor antagonists reduced concentration-dependently the adenosine-induced vasoconstriction. Denudation of the endothelial layer reduced the adenosine and the NECA-induced contractions by 50-70%. Furthermore, indomethacin reduced concentration-dependently the adenosine or the NECA-induced contractions in intact and endothelium-denuded rings. A thromboxane receptor antagonist blocked the adenosine and NECA-induced contractions in intact and endothelium-denuded rings, suggesting the involvement of an arachidonic acid metabolite as the mediator of the vasoconstriction. We propose that adenosine A_2B receptors mediate the adenosine-induced contraction vasomotor effect in human chorionic vessels, and that it involves the synthesis of a thromboxane receptor activator or a related prostanoid.