A recent article supports the concept that prostaglandin (PG)E(2) EP(1)-receptor antagonists reduce stroke severity and cell damage; could these agents become a substitute for cyclooxygenase (COX)-2 inhibitors? The total activity of COXs--rate-limiting enzymes of PGE(2) synthesis--increases following acute neurological insult. Drugs that offer the beneficial anti-inflammatory and neuroprotective effects of PGs but that limit the negative effects of COX-2 inhibition could provide the next generation of treatment for acute neuronal damage.