The present work uses and extends a dynamic mathematical model [J. L. Bert, B. D. Bowen, and R. K. Reed. Am. J. Physiol. 254 (Heart Circ. Physiol. 23): H384-H399, 1988] to investigate microvascular exchange and interstitial fluid volume regulation in the rat. Alternative concepts of transcapillary exchange as well as other parametric changes were incorporated into the model. In all cases, predictions resulting from these changes did not describe the available experimental information as well as the original model. A sensitivity analysis of the model showed the microvascular exchange system to be well regulated near its normal steady-state conditions through passive readjustment of the forces participating in the volume regulation. The transient rates of fluid and protein exchange were studied in order to determine the mechanisms inherent in the model that lead to fluid volume regulation during episodes of increased venous pressure and hypoproteinemia. In addition to interstitial compliance, lymph flow characteristics, and washdown of interstitial proteins, it was found that the magnitude and direction of reabsorption played an important role in the regulation process. Edema was always associated with a permanent reversal of the reabsorptive flow.