New daily hemodialysis therapies operate at low dialysate flow rates to minimize dialysate volume requirements; however, the dependence of dialyzer clearances and mass transfer-area coefficients for small solutes on dialysate flow rate under these conditions have not been studied extensively. We evaluated in vitro dialyzer clearances for urea and creatinine at dialysate flow rates of 40, 80, 120, 160, and 200 ml/min and ultrafiltration flow rates of 0, 1, and 2 l/h, using a dialyzer containing PUREMA membranes (NxStage Medical, Lawrence, MA). Clearances were measured directly across the dialyzer by perfusing bovine blood with added urea and creatinine single pass through the dialyzer at a nominal blood flow rate of 400 ml/min. Limited, additional studies were performed with the use of dialyzers containing PUREMA membranes at a blood flow rate of 200 ml/min and also with the use of other dialyzers containing polysulfone membranes (Optiflux 160NR, FMC-NA, Ogden, UT) and dialyzers containing Synphan membranes (NxStage Medical). For dialyzers containing PUREMA membranes, urea and creatinine clearances increased (p < 0.001) with increasing dialysate and ultrafiltration flow rates but were not different at blood flow rates of 200 and 400 ml/min. Dialysate saturation, defined as dialysate outlet concentration divided by blood water inlet concentration, for urea and creatinine was independent of blood and ultrafiltration flow rate but varied inversely (p < 0.001) with dialysate flow rate. Mass transfer-area coefficients for urea and creatinine were independent of blood and ultrafiltration flow rate but decreased (p < 0.001) with decreasing dialysate flow rate. Calculated mass transfer-area coefficients at low dialysate flow rates for all dialyzers tested were substantially lower than those reported by the manufacturers under conventional conditions. We conclude that dialyzers require specific characterization under relevant conditions if they are used in novel daily hemodialysis therapies at low dialysate flow rate.