In normal kidneys the renal medulla very efficiently converts arachidonic acid to prostaglandins. Although the renal cortex has only trace amounts of cyclooxygenase activity, we report here the existence of an active cortical NADPH-dependent monooxygenase that converts arachidonate primarily into 19-hydroxy- and 20-hydroxyarachidonate as well as 19-ketoarachidonate and a dicarboxylic acid. The enzyme is presumably a cytochrome P-450 monooxygenase and demonstrated marked resistance to inhibition by 2-diethylaminoethyl-2,2-diphenylvalerate hydrochloride (SKF-525A), metyrapone, and carbon monoxide. In the rabbit kidney these products are produced only by the cortex in the presence of NADPH and represent the major metabolic products of arachidonate metabolism.