of cyclooxygenase isoform activity and prostanoid production in normal and diseased Han:SPRD-cy rat kidneys. Am J Physiol Renal Physiol 290: F897-F904, 2006. First published October 18, 2005 doi:10.1152/ajprenal.00332.2005.-Renal prostanoids are important regulators of normal renal function and maintenance of renal homeostasis. In diseased kidneys, renal cylooxygenase (COX) expression and prostanoid formation are altered. With the use of the Han:Sprague-Dawley-cy rat, the aim of this study was to determine the relative contribution of renal COX isoforms (protein, gene expression, and activity) on renal prostanoid production [thromboxane B 2 (TXB2, stable metabolite of TXA2), prostaglandin E2 (PGE2), and 6-keto-prostaglandin F1␣ (6-keto-PGF1␣, stable metabolite of PGI 2)] in normal and diseased kidneys. In diseased kidneys, COX-1-immunoreactive protein and mRNA levels were higher and COX-2 levels were lower compared with normal kidneys. In contrast, COX activities were higher in diseased compared with normal kidneys for both COX-1 [0.05 Ϯ 0.02 vs. 0.45 Ϯ 0.11 ng prostanoids ⅐ min Ϫ1 ⅐ mg protein Ϫ1 (P Ͻ 0.001)] and COX-2 [0.64 Ϯ 0.10 vs. 2.32 Ϯ 0.22 ng prostanoids ⅐ min Ϫ1 ⅐ mg protein Ϫ1 (P Ͻ 0.001)]. As the relative difference in activity was greater for COX-1, the ratio of COX-1/COX-2 was higher in diseased compared with normal kidneys, although the predominant activity was still due to the COX-2 isoform in both genotypes. Endogenous and steady-state in vitro levels of prostanoids were ϳ2-10 times higher in diseased compared with normal kidneys. The differences between normal and diseased kidney prostanoids were in the order of TXB 2 Ͼ 6-keto-PGF 1␣ Ͼ PGE2, as determined by higher renal prostanoid levels and COX activity ratios of TXB 2/6-keto-PGF1␣, TXB2/PGE2, and 6-keto-PGF 1␣/PGE2. This specificity in both the COX isoform type and for the prostanoids produced has implications for normal and diseased kidneys in treatments involving selective inhibition of COX isoforms. thromboxane; prostaglandin CYCLOOXYGENASE (COX