THE APPRECIATION that two oxygenated metabolites of arachidonic acid, prostacyclin (PGI2) and thromboxane A2 (TxA2), have potent and contrasting effects on vascular tone and platelet function in vitro has prompted attempts to define their importance in human vascular disease. Both compounds are formed from arachidonic acid by the enzyme cyclooxygenase via cyclic endoperoxide intermediates, PGG2 and PGH2. TxA2, the major cyclooxygenase product in the platelet, is a vasoconstrictor and potent stimulus to platelet aggregation in vitro. I PGJ2, a vasodilator and inhibitor of platelet aggregation, is the predominant product of the same enzyme in vascular endothelial cells. 2 The development of techniques to study platelet function in vivo3 4 and ex vivo5 preceded the discovery of these compounds, and the application of these tests suggests that increased platelet activation may well accompany vascular occlusive events in man. 4 6 Thus, it seems reasonable that PGI2 and TxA2 might play an important role in this and other syndromes of disordered platelet-vascular homeostasis in man. 7 Support for this concept relies upon the develop-ment of methods to measure PGI2 and TxA2 in human biological fluids. However, both PGI2 and TxA2 have extremely short half-lives'2 and are rapidly cleared from the bloodstream. Furthermore, arachidonic acid release from biological membranes (and thus synthesis of PGI2 and TxA2) is likely to be phasic rather than continuous. This phenomenon also renders measurement of these products highly liable to artifact when performed in media obtained by invasive sampling techniques, such as plasma. Finally, thereare the technical difficulties involved in devising assays of requisite sensitivity and specificity. Three approaches have been used: bioassay, ra-dioimmunoassay (RIA) and stable isotope dilution assays involving gas chromatography-mass spectrometry (GC/MS). Bioassays have the advantage of actually measuring biological activity and have been of critical qualitative importance in the discovery of pros-taglandins, 2, 8 Because of the evanescence of both PGI2 and TxA2 in the circulation, RIAs and GC/MS methods are directed toward metabolites. These methods are more sensitive and specific than bioassay and more applicable to quantitative study of prostaglandin turn-over in man. Initially, the various approaches appeared