The contractile effect of ATP given alone or in the presence of other nucleotides was studied in rat aortic strips. A sustained contraction in response to ATP (30 μM to 10 mM) was observed during UTP exposure instead of the fast transient contraction produced via P 2X purinoceptor activation in the absence of UTP, and contrary to the relaxation elicited when the tone had been raised by noradrenaline and KCl. This sustained ATP effect was produced in the smooth muscle and not via the same mechanism through which UTP elicited contraction, since the contractions in response to UTP and ATP were additive. They were also coupled to different transduction pathways: the effect of UTP but not that of ATP was pertussis toxin-sensitive. In contrast to the fast transient ATP contraction during basal tone, the sustained response was not desensitized by α, β-methylene ATP exposure (30 μM), but was inhibited by reactive blue 2 (10 and 30 μM). Among the nucleotides assayed, UDP and ATP γS also enabled ATP to elicit a sustained contraction. ADP, AMP, dATP, 2-methylthio ATP, α, β-methylene ATP, GTP, GDP, GMP, CTP and ITP also induced a sustained contraction in the presence of UTP. However, adenosine (1 mM) and adenine (0.3 to 3 mM) induced relaxation when the tone had been raised by UTP. According to these results a non-selective nucleotide receptor, different from the P 2 purinoceptors functionally characterized so far, seems to mediate sustained contractions in rat aortic strips in the presence of UTP, UDP or ATP γS.