Inhibitors of prostaglandin synthesis such as indomethacin and meclofenamate may attenuate the diuretic response to furosemide. The purpose of the present study was to clarify whether an inhibition of furosemide's action in the loop of Henle is involved in this interaction. In a first set of experiments, the effect of indomethacin and meclofenamate on the diuretic response to furosemide was re-evaluated in anaesthetized rats. Single loops of Henle of rat kidneys were perfused in vivo in a second group of rats. Furosemide was added to the perfusion fluid and the effect of indomethacin (5 mg/kg i.v.) and meclofenamate (5 mg/kg i.v.) on furosemide's action in the loops was tested. In the absence of furosemide, indomethacin and meclofenamate did not significantly affect urine flow and sodium chloride excretion, or the loop's sodium and chloride reabsorption. Both prostaglandin inhibitors, however, significantly attenuated the diuretic effect of furosemide (1 mg/kg i.v.) and the inhibitory action of the diuretic, at a concentration of 10(-4) M, on the loop's sodium and chloride transport. The results identify the loop of Henle as a tubular site of interaction between furosemide and prostaglandin inhibitors. The interaction may be related to a furosemide-induced stimulation of renal prostaglandins.