Urea rebound has been documented to occur after hemodialysis, but the magnitude and causes are not clearly defined. In this study we evaluated the effect of high-flux hemodialysis on urea rebound and Kt/V. Blood urea nitrogen samples were obtained before, immediately after, and 30 minutes after hemodialysis in 49 patients. Rebound was evaluated with respect to dialysis efficiency, dialysis treatment time, the occurrence of hypotension, and hematocrit. Urea rebound was significant and resulted in an overall decrease in Kt/V from 1.2 +/- 0.3 to 1.0 +/- 0.2 (P < 0.001). Of the 45 patients with a measured Kt/V of greater than 1.0, 40% had an actual delivered Kt/V of less than 1.0 once rebound was taken into account. Urea rebound correlated strongly with dialysis efficiency but not with hypotension, suggesting that rebound resulted primarily from delayed urea mass transfer across cell membranes. We conclude that increasing dialysis efficiency increases urea rebound and increases the error in Kt/V determinations from single pool urea kinetics.