Cyclooxygenase (COX)-2 mRNA and immunoreactive protein localize to the macula densa and adjacent cortical thick ascending limb in renal cortex, and chronic NaCl restriction increases expression of this enzyme. These findings suggest an integral role for eicosanoids generated by macula densa-associated COX-2 in mediating renin release. As selective inhibitors of COX-2 become available, it will be important to assess their effects on the renin-angiotensin system and glomerular hemodynamics.