The effect of ethacrynic acid (EA) on the renal secretion of PAH was examined in cat kidney. C<sub>PAH</sub> and T<sub>PAH</sub> were measured before and after infusion of EA (0.5 ~ 50mg/kg) through the femoral vein. The following results were obtained: 1) In the dosage range of 0.5 to 25 mg/kg, EA increased the urine flow, and sodium and potassium excretion in dose-dependent manner, but the glomelular filtration rate was decreased as the dosage of EA was increased. 2) C<sub>PAH</sub> and T<sub>PAH</sub> were decreased by EA in the dosage range of 3 to 25 mg/kg and 1 to 50 mg/kg, respectively, in dose¡¤dependent manner with the dosage to cause 50% inhibition of about 5 mg/kg. 3) With dosage of 0.5mg/kg, EA appeared to exert a great effect on diuretic response without the influence on T<sub>PAH</sub>. At 10min after infusion of EA, a potent diuretic effect appeared, while T<sub>PAH</sub> did not show a significant change. These results suggest that the action mechanism of EA on tubular secretion of PAH may be different from that on natriuresis. 4) With dosage of 5 mg/kg, EA did not inhibit the Na-K-ATPase activity in microsomal fractions from both cortex and medulla. 5) The double reciprocal plot (l/T<sub>PAH</sub> versus l/P<sub>PAH</sub>) suggested that EA inhibited the P AH secretion by a competitive pattern. However, probenecid, a prototypic inhibitor of the organic acid pump, had no influence on both the inhibitory effect of T<sub>PAH</sub> and the natriuretic effect by EA. These results suggest that in vivo EA altered tubular secretion of P AH through interactions with receptors that are not identical with the Na-K-ATPase.