Of the naturally-occurring cyclo-oxygenase metabolites known as the prostaglandins, three such products, prostaglandin E₁, prostaglandin D₂ and prostacyclin have been demonstrated to exert potent anti-aggregating actions on platelets. Early studies indicated that prostaglandin E₁ (PGE₁) which is derived from the precursor fatty acid, dihomo-gamma-linoleic acid, could inhibit platelet aggregation in vitro in platelet-rich plasma (PRP) from several species (1,2,3). However, since only trace levels of PGE₁ can be detected under normal dietary conditions in vivo (A), the physiological significance of the actions of this prostanoid remain obscure. Later studies with PGD₂ (Fig 1) derived from the essential fatty acid arachidonic acid, likewise indicated this prostanoid to be a potent inhibitor of platelet aggregation in human platelet-rich plasma in vitro (5,6). In contrast to PGE₁, the activity of PGD₂ could not be readily demonstrated in the plasma of the rat or rabbit (7). Thus PGD₂ is a potent inhibitor of platelet aggregation in human, sheep and horse platelet-rich plasma but only a weak inhibitor in dog, rabbit, guinea-pig and rat plasma (Table 1). PGD₂ can be generated by human platelets and has been detected in human plasma (8,9,10), while the non-enzymatic conversion of the endoperoxide PGH₂ to PGD₂ is greatly enhanced by the presence of plasma protein from certain species including man (11,12).