The dynamic distribution of intravenously infused solutions between the plasma and the interstitial compartments was studied. A mathematical model developed to simulate infusion experiments considered transcapillary fluid and protein exchange, lymph flow, interstitial compliance, capillary surface area, and peripheral vascular resistance. The experimental arterial and venous blood pressure responses and the infusion rate were used as forcing functions. A piecewise optimization procedure resulted in excellent agreement between the simulated and experimental plasma volume responses and provided reasonable time-varying behavior for the precapillary-postcapillary resistance ratio and the capillary surface area. The model was tested with experimental data collected by infusing isotonic Tyrode's or dextran solution into nephrectomized dogs. Blood volume was measured continuously by giving a single injection of 51 Cr-labeled red cells and monitoring the blood radioactivity as it passed through an extracorporeal shunt. The model predicted qualitatively different responses for the precapillary-postcapillary resistance ratio depending on the type of solution infused and the value assumed for tissue compliance. Further analysis indicated that the assumption of a tissue space with overall high compliance (approximately 100 ml/kg mm Hfj-1 ) is more realistic than are the much lower compliances previously reported. Parametric studies revealed that the capillary surface area, the precapillary-postcapillary resistance ratio, and the tissue compliance, but not the lymph flow or the transcapillary protein movement, exert a strong influence on the short-term plasma retention of infused fluids.KEY WORDS mathematical precapillary-postcapillary resistance ratio tissue compliance model transcapillary exchange optimization blood volume• It is becoming increasingly apparent that transcapillary fluid exchange plays an important role in both the short-term control of plasma volume (1) and the control of the entire extracellular fluid space (2). In situations such as hemorrhage, exercise, standing, fluid replacement therapy, or hemodialysis therapy, in which there are rapid adjustments in circulatory volume, the Starling fluid shift mechanism is the major short-term source of plasma volume control. Although considerable research has been done on plasma-interstitial fluid exchange following hemorrhage, there is relatively little information available on the reverse problem From the Department of Physiology and the Bioengineering Program,