BACKGROUND Ultrafiltration (UF) is assumed to enhance urea removal during haemodialysis (HD) because of convective transport and because of contraction of urea distribution volume. However, UF-induced blood volume reduction has been hypothesized to enhance peripheral urea sequestration and post-dialysis urea rebound (PDUR), possibly reducing HD effectiveness. The effect of UF on PDUR was investigated in this study. METHODS Nine HD patients were studied on two subsequent treatment days. The first HD was performed with UF (UF-rate=0.78+/-0.27 l/h), and the second treatment without UF. Serial measurements of serum water urea nitrogen concentration, arterial blood pressures (BP), and relative blood volume changes (BV%) were obtained over the duration of HD. RESULTS BP and BV% decreased with UF (BP(sys)= -9%, BP(dia)=-8%, BP(mean)=-9%, BV%=-15%) but increased or remained unchanged without UF (BP(sys)= 9%, BP(dia)=12%, BP(mean)=11%, BV%=1%). PDUR was 28.6+/-9.6% without UF, and increased in every single patient with UF (40.7+/-13.2%, P<0.01). Modelled perfusion of the peripheral low-flow compartment decreased from 1.45+/-0.54 l/min without UF to 0.91+/-42 l/min with UF (P<0.05), thereby explaining an enhanced two-compartment effect and increasing PDUR. CONCLUSIONS The significant increase in the two-compartment effect of urea kinetics observed in current HD accompanied by UF can be explained by compensatory, intradialytic blood flow redistribution induced by blood volume reduction. Because of the link between UF and blood flow, limited solute clearance treatment modes that optimize fluid removal such as variable UF will also have favourable effects on delivered dose of dialysis.