The expression of mRNAs for three P2X receptor subtypes (PX21, P2X2, P2X4) in the rat vascular system was studied by in situ hybridization and RT-PCR. In heart sections mRNAs transcripts for all three receptors were colocalized in smooth muscle cells of coronary vessels, while no specific positivity was apparent in myocardium. Coexpression of P2X receptor mRNA transcripts were also observed in other peripheral vessels, including aorta, pulmonary artery, internal and external iliac arteries, renal artery and femoral artery. By contrast, no mRNA transcripts of the above receptors were found in the superior mesenteric artery. RT-PCR performed on microdissected tissues (coronary arteries, aorta and myocardium from various heart areas) confirmed the presence of P2X1, P2X2 and P2X4 receptor mRNAs. Furthermore, in the same tissues two splice variants of the P2X2 receptor were identified. These results reveal an important molecular heterogeneity of P2X receptors, thus substantiating the possibility of a heteropolymeric assembly of ATP-gated ion channels in the cardiovascular system.