Two new radioligands for the TXA2 receptor, [3H]S-145 (5Z-7-(3-endo-[( ring-4-3H]phenyl)sulphonylamino- [2.2.1.]bicyclohept-2-exo-yl) heptenoic acid) and [125I]I-S-145-OH (5Z-7-(3-endo[( 125I] 3-iodo-4-hydroxyphenylsulphonyl)amino- [2.2.1.] bicyclohept-2- yl)heptenoic acid) were synthesized and their binding to washed human platelets, platelet membrane and solubilized TXA2 receptor was examined. Both [3H]S-145 and [125I]I-S-145-OH bound to the above preparations in a saturable and reversible manner. In contrast to the conventional TXA2 receptor ligands, such as [3H]U-46619 and [125I]PTA-OH, nonspecific binding of these radioligands constituted less than 10% of the total binding under the standard assay conditions. Scatchard analysis revealed a single class of binding sites for all three preparations; the Kd values of the [3H]S-145 binding were 3.64, 3.14 and 8.22 nM for washed platelets, platelet membrane and the solubilized receptor, respectively, and those of [125I]I-S-145-OH binding were 5.72 and 4.09 nM for washed platelets and the solubilized receptor, respectively. Thus, [3H]S-145 and [125I]I-S-145-OH are the ligands with low nonspecific binding and the highest affinities for the TXA2 receptor, which are independent of membrane preparation and receptor solubilization. In addition, the alpha-carboxyl group of S-145 could be modified without change in the binding affinity.