Francois Nantel (Merck Frosst) described work characterizing the regulation of cyclooxygenase-2 (COX-2) at the RNA, protein, and mediator (PGE2) level in two similar models: the rat carrageenin-induced edema model and the rat carrageenininduced hyperalgesia model. In both models, carrageenin induced both mRNA and protein levels of COX-2 along with PGE2 levels. Interestingly, indomethacin completely abolished this induction in the edema model which suggests the existence of some positive feedback loop by which PGE2 acts to regulate COX-2 expression. However, indomethacin had no effect on these levels in the model of hyperalgesia. Immunoreactivity towards COX-2 was only detected in the epidermis in the edema model where the hyperalgesia model also showed immunoreactivity in skeletal muscle and inflammatory cells. Differences in the amount of carrageenin administered in the two models along with an age difference in the rats used may explain these observations.