Background:Little is known about cellular mechanisms that actively lower the levels of the proinflammatory enzyme COX-2. Results: An interaction between COX-2 and the prostaglandin receptor EP 1 facilitates the degradation of COX-2 through the proteasome. Conclusion: EP 1 negatively regulates COX-2 expression. Significance: Receptor-mediated regulation of COX-2 presents an important means of moderating inflammation and resolution of pathophysiological events.