Chronic fluid overload and hypertension are highly prevalent in the dialysis population. Measurement of blood volume (BV) during hemodialysis (HD) may prove useful to achieve dry weight (DW). Twelve (12) chronic hemodynamically stable dialysis patients were randomly selected to participate in a pilot study. BV changes were measured using an online blood volume monitor (Hemoscan, Gambro AB, Stockholm, Sweden). As part of an initial observation phase, the magnitude of BV variation (deltaBV) in percentage and total UF volume (UF) in liters were recorded for each dialysis session, and the deltaBV/UF ratio was calculated. DW was subsequently reduced by 0.5 kg in all patients and the tolerance of the procedure was assessed. Attempted DW reduction was successful in seven patients, whereas it resulted in hypotension or symptoms in the other five cases. The deltaBV/UF ratio was found to be significantly lower in patients in whom attempted DW reduction was successful (2.47%/L vs. 3.45%/L, P < 0.05). Using receiver operating characteristic (ROC) curve analysis, a deltaBV/UF ratio of less than 2.6%/L offered the best overall prediction of successful DW reduction. These results suggest that measurement of BV changes during HD and calculation of the deltaBV/UF ratio are valuable tools for management of DW in clinically stable patients.