The regional blood flow model predicts that urea sequestration occurs in organs rather than cells, and that post-dialysis urea rebound is a function of both cardiac index (CI) and regional blood flow distribution to muscle. We measured cardiac output (CO) in 100 randomly selected dialysis patients using bioelectric impedance three times during a single dialysis. Mean CO was 5.8 +/- 2.1 liter/min and CI averaged 3.1 +/- 1.1 liter/min/M2. CI was negatively correlated with age (r = -0.48, P < 0.01). CI was strongly affected by vasodilator ingestion (yes, N = 36, CI = 3.5 +/- 1.2; no, N = 64, CI = 2.88 +/- 0.92, P < 0.006). CI was not associated with systolic, diastolic, or mean blood pressures, nor with Hct, although very few severely anemic patients were in the cohort. Repeat intra-dialytic CO measurements two to three months later in 15 patients with low CI (2.59 +/- 0.59 liter/min/M2) and in 13 patients with high CI (5.00 +/- 0.9, P < 0.001) during a urea kinetic modeling session including 30 minutes post-dialysis rebound, sampling showed highly reproducible values for CO, with a mean absolute value % difference between CO values measured several months apart of 9.0 +/- 17%, r = 0.92. Urea rebound expressed as the difference (delta Kt/V30) between equilibrated and single-pool Kt/V was lower in the high CI group (-0.099 +/- 0.07) than in the low CI group (-0.16 +/- 0.06, P = 0.026), and delta KT/V30 as well as delta Kt/V30 divided by K/V correlated with CI (r = 0.48 and 0.48, respectively, P < 0.01). The RBF model was used to compute a group mean predicted delta Kt/V30 for the low CI and high CI groups based on measured group mean values for CI and K/V. The predicted delta Kt/V30 values for the high CI group (-0.097) and the low CI group (-0.183) agreed closely with measured values. RBF modeled values of CO (7.46 +/- 2.96 liter/min) were not significantly different from impedance-derived CO (6.93 +/- 2.70 liter/min), and the two CO measures correlated significantly (r = 0.63, P = 0.0003). The results provide support for the regional blood flow model of urea kinetics.