Using prostaglandin H₂ (PGH₂) as a structural model for rationally designed cyclooxygenase inhibitors, a series of 7-oxabicyclo[2.2.1]heptanes were prepared. Although none of the initial compounds inhibited cyclooxygenase, a number of the compounds inhibited arachidonic acid-induced human platelet aggregation. Further investigation with this group of platelet inhibitors led to the identification of extremely potent prostaglandin D₂ (PGD₂) agonists, thromboxane A₂ (TxA₂) agonists, TxA₂ antagonists, and cyclooxygenase inhibitors. This review will outline the structure-activity relationships in each of these series of compounds.