Dialyzer clearance depends on blood and dialysate flow rates and the product of the membrane surface area and mass transfer coefficient for the solute of interest, K(o)A. K(o)A is usually assumed to be constant for a given dialyzer and solute. Results of two recent studies challenge this assumption. Therefore, we examined the hypothesis that K(o)A depends on blood and dialysate flow rates during clinical dialysis. Urea clearances were measured for two different dialyzers at all four combinations of two blood flow rates (300 and 400 mL/min) and two dialysate flow rates (500 and 800 mL/min). Urea K(o)A was calculated by using standard equations for mass transfer in dialyzers operated with countercurrent flows. The impact of blood and dialysate flow rates on K(o)A was assessed by analysis of variance. Increasing dialysate flow rate from 500 to 800 mL/min significantly increased K(o)A (P = 0.018). Increasing blood flow rate from 300 to 400 mL/min did not significantly increase K(o)A (P = 0.083). Also, K(o)A decreased significantly with increasing hematocrit (P = 0.022). The results of this study extend previous in vitro findings by showing that increasing the dialysate flow rate increases urea K(o)A during clinical dialysis. However, the increase in K(o)A observed during clinical dialysis (5.7%) is less than that previously reported in vitro (14.7%), possibly because of the impact of blood cells and proteins on blood-side mass transfer resistance.