Treprostinil, a prostacyclin analogue, is used to treat pulmonary hypertension. However, the mechanism of action whereby this drug modifies the pathophysiological status may involve more than prostacyclin (IP) receptors, as Whittle et al (2012) have shown that it activates human recombinant prostanoid DP1, EP2 and IP receptors. In view of the recent emergence of highly selective EP2 receptor antagonists (e.g. PF-04418948; Forselles et al., 2011), it was decided to determine whether our current armoury of prostanoid antagonists was adequate to elucidate the complex pharmacology of treprostinil. Treprostinil lacks the ether oxygen moiety at C6-9 present in prostacyclin (PGI2) and has a benzene ring inserted in its α-chain. Naxaprostene also has both functionalities and we decided to compare its inhibitory profile with that of treprostinil. In the current study, we have used isolated preparations of rabbit saphenous vein (rSV) and inferior vena cava (rVC). 5 mm rings were dissected from male rabbits (1.5-2.5 kg) and were mounted under isometric conditions (resting tension of 0.75 – 1.0 g) in 10 ml baths at 37°C. Contractions were elicited by adding histamine and phenylephrine (300-600 nM) respectively. We have used BW-245C, ONO-AE1-259, TCS-2510 and AFP-07 as selective DP1, EP2, EP4 and IP agonists respectively. The corresponding antagonists were BW-A868C and MK-0524, ACA-23 (same series as PF-04418948), GW-627368 and RO-1138452 (Jones et al., 2009). A simple antagonist reversal protocol showed that both preparations contain inhibitory DP1, EP2, EP4 and IP receptors. In further experiments, preparations were pretreated with 3 of the antagonists (e.g. BW-A868C / ACA-23 / GW-627368), followed by cumulative doses of treprostinil or naxaprostene and finallyfollowed by the fourth antagonist (CAY-10441) in an attempt to reverse the relaxation. In this way we could apportion DP1, EP2 and IP agonism to treprostinil, but only IP agonism to naxaprostene. In some preparations naxaprostene behaved as a partial agonist. The relevance of these findings to the therapeutic use of prostacyclin analogues will be discussed.