To investigate changes in destruction-replenishment curves (in vitro and in vivo) that result from microbubble destruction in feeding vessels that pass through the imaging plane before microbubbles enter the region of interest (ROI). During continuous injections of an ultrasonographic contrast agent, nonlinear gray-scale images were obtained in vitro in the longitudinal plane of a renal dialysis cartridge flow phantom (flow rates of 100, 200, and 400 mL/min) and in vivo in the coronal plane of the left kidneys of two rabbits (two kidneys). Destruction-replenishment curves were obtained for the dialysis cartridge in ROIs located immediately after the entrance of the microbubbles into the image plane and further from the entrance, after microbubbles had traveled across the complete length of the imaging plane. Replenishment curves were also obtained from ROIs in the rabbit kidneys at the level of segmental arteries, distal interlobar arteries, and the cortex. The ROIs immediately after the entrance of the microbubbles in the image plane of the dialysis cartridge and in the segmental artery of the kidney followed a typical exponential function, A(1 - e-alphat). Early portions of curves obtained in ROIs filled with microbubbles that had already passed through the image plane of the dialysis cartridge or in the renal cortex were not well described by such a function. The shape of the curve and the variations as a function of flow rate can be explained by means of a mathematical model based on indicator-dilution theory. When the feeding vessels of an ROI travel across the ultrasound field before they reach the measurement region, the typical shape of the replenishment curve is modified (reduced velocity parameter and plateau).