At the beginning of hemodialysis (HD), urea in arterial blood drops rapidly, whereas a pronounced postdialytic urea rebound (PDUR) can be observed when HD is discontinued. In a new approach to this observation, the authors suggest that solute flux from remote body compartments to the dialyzer is governed by 1) diffusion of solutes from the tissue to the blood perfusing the tissue, and 2) by regional blood flow distribution, cardiopulmonary recirculation, and access recirculation, respectively. These concepts were incorporated into a variable volume, two compartment model that could be treated as an eigenvalue problem and solved analytically. The resulting equations were used to model intradialytic and postdialytic urea profiles with the help of a commercial spreadsheet program. The significance of hemodynamic model parameters such as cardiac output (CO) and regional blood flow distribution on PDUR was modeled in simulation runs, where PDUR increased from 5% to 15% when CO fell from 7 to 3 l/min with standard treatment parameters (t = 3h, KD = 0.3 l/min, V = 35l, UFV = 2.8l, fQHFS = 0.8, QAc = 0.8l/min). Thus, this urea kinetic model establishes a previously missing link between hemodynamics and solute removal.