The dialyzer mass transfer-area coefficient (KoA) for area is an important determinant of urea removal during hemodialysis and is considered to be constant for a given dialyzer. We determined urea clearance for 22 different models of commercial hollow fiber dialyzers (N = approximately 5/model, total N = 107) in vitro at 37 degrees C for three countercurrent blood (Qb) and dialysate (Qd) flow rate combinations. A standard bicarbonate dialysis solution was used in both the blood and dialysate flow pathways, and clearances were calculated from urea concentrations in the input and output flows on both the blood and dialysate sides. Urea KoA values, calculated from the mean of the blood and dialysate side clearances, varied between 520 and 1230 ml/min depending on the dialyzer model, but the effect of blood and dialysate flow rate on urea KoA was similar for each. Urea KoA did not change (690 +/- 160 vs. 680 +/- 140 ml/min, P = NS) when Qh increased from 306 +/- 7 to 459 +/- 10 ml/min at a nominal Qd of 500 ml/min. When Qd increased from 504 +/- 6 to 819 +/- 8 ml/min at a nominal Qh of 450 ml/min, however, urea KoA increased (P < 0.001) by 14 +/- 7% (range 3 to 33%, depending on the dialyzer model) to 780 +/- 150 ml/min. These data demonstrate that increasing nominal Qd from 500 to 800 ml/min alters the mass transfer characteristics of hollow fiber hemodialyzers and results in a larger increase in area clearance than predicted assuming a constant KoA.