The pharmacokinetics and pharmacodynamics of furosemide were evaluated after intravenous administration of the same total dose of furosemide in different lengths of infusion time (10 seconds, 30 min, 2 and 8 hr) to six dogs. The fluid loss in urine was immediately replaced volume for volume with intravenous infusion of lactated Ringer's solution. The pharmacokinetic parameters such as percent of the dose excreted in urine, total body and renal clearances, and terminal half-life were not significantly different with 4 different infusion times. The volume of distribution at steady state and mean residence time based on venous data, on the other hand, appeared to increase with increasing infusion time. The mean values for Vss were 0.334, 0.478, 0.499 and 0.708 1/㎏ for 10 seconds, 30 min, 2 hr and 8 hr of infusion, respectively and the corresponding values for MRT were 17.5, 22.2, 24.8 and 38.1 min. The diuretic effects (urine output and urinary excretion of sodium) were generally found to increase with increasing infusion times; the total mean 24 hr urine outputs were 1,102, 1,464, 2,190 and 3,470 ㎖ for 10 seconds, 30 min, 2 hr and 8 hr or infusion, respectively, and the corresponding values for sodium excretion were 170, 175, 272, and 440 mmol. Furosemide plasma concentrations and hourly urinary excretion rates of furosemide, sodium and potassium during the apparent steady state (between 2-8 hr) in the 8 hr infusion study were fairly constant. Effects of differences in the rate and composition of intravenous fluid replacement for urine loss on the pharmacokinetics and pharmacodynamics of furosemide were evaluated using dog as a model animal. Each of 6 dogs rececived 8-hr constant intravenous infusion of 20㎎(15㎎ used in one dog) of furosemide with 0% replacement (treatment I), 50% replacement (treatment II ) and 100 replacement (treatment III) with lactated Ringer's solution as well as with 100 replacement with 5% dextrose in water (treatment IV). Most of pharmacokinetic parameters such as plasma clearance, steady state volume of distribution, mean residence time and terminal half life were essentially the same in all 4 treatments. Renal clearances and urinary excretion rates of the drug in treatments II, III and IV were essentially the same, but about 20% higher than those in treatment I. In spite of the similarities in kinetic properties, diuretic and/or natriuretic effects from furosemide were, however, markedly different among the 4 treatments. For example, mean 10 hr urine outputs were 646, 1,046, 3,156 and 1,976 ㎖and mean 10 hr sodium excretions were 87.0, 142, 383 and 97.2 mmol for treatments I-IV, respectively. Except for treatment III, diuresis and/or natriuresis were found to be time-dependent, generally decreasing with time until reaching a low plateau during later hours of infusion. The present findings also showed that (a) no fluid replacement and 100% replacement with 5% dextrose solution both produced the same degree of severe acute tolerance in natriuresis indicating the insignificance of water compensation in tolerance development; (b) in treatment II where neutral sodium balance was achieved, the development of acute tolerance in diuresis and natriuresis can mainly be attributed to negative water balance under this special condition: ⓒ at steady state the hourly diuresis and natriuresis could differ up to about 10 times between treatments. Some implications in kinetic/dynamic relationship or modeling, in the clinical use and in the bioequivalency evaluation of dosage forms are discussed.