BACKGROUND: The renal effects of cyclooxygenase-2 (COX-2) inhibitors have been incompletely elucidated, and acute renal failure (ARF) due to COX-2 inhibitors has been reported. METHODS: In order to determine the causes of ARF and hyperkalaemia in five patients during COX-2 inhibitor therapy, we carefully analysed case studies of consecutive in-patients or out-patients referred to our Renal Division over a 6-month period for ARF and hyperkalaemia who had recently received COX-2 inhibitors. RESULTS: ARF developed 2-3 weeks after COX-2 inhibitor therapy in five patients. The ARF was consistent with pre-renal azotaemia from renal hypoperfusion. Four patients were receiving the loop diuretic, furosemide. Four patients developed hyperkalaemia and decreased serum bicarbonate despite diuretic therapy, and one patient had changes in plasma renin activity and aldosterone levels consistent with reversible hyporeninaemic hypoaldosteronism. Renal failure was reversible after discontinuation of diuretics and COX-2 inhibitors. CONCLUSIONS: COX-2 inhibitors may cause reversible ARF and hyperkalaemia in patients with oedematous conditions treated with low sodium diets and loop diuretics.