The urinary excretion of prostaglandins (PG) E2 and F2 alpha, which reflects the renal synthesis of these substances, was evaluated by radioimmunoassay before and after an i.v. injection of furosemide in 10 normal subjects and in 10 patients with essential hypertension. In most normal subjects, urinary PGE2 increased after furosemide injection, whereas PGF2 alpha decreased to undetectable levels. In the hypertensive subjects, PGE2 increased to a lesser degree or decreased, but PGF2 alpha excretion was unchanged or augmented. These results suggest that furosemide may increase PGE2 synthesis not only by increasing the availability of the substrate arachidonic acid or by inhibiting the action of the catabolizing enzyme 15-hydroxyl-PG-dehydrogenase, as has been proposed, but also by depressing the activity of the enzyme PGE2-9-ketoreductase, which catalyzes the conversion of PGE2 to PGF2 alpha. In essential hypertension, an increased activity of PGE2-9-ketoreductase could explain the decreased levels of PGE2 that have recently been described in these patients. Whether these abnormalities in PG interconversion play a role in the pathogenesis of the hypertensive state or are secondary to it remains a question for further investigation.