Hypertonic saline-dextran (HSD) solutions have been used for hemorrhagic shock, aortic aneurysm, and cardiopulmonary bypass surgery (CPB). Jehovah's Witness patients refuse blood and derivatives even under life-threatening conditions. A negative fluid balance for Jehovah's Witnesses would avoid further hemodilution. In this study we compared clinical, hemodynamic, laboratory evolution, and fluid balance of 20 Jehovah's Witnesses over the first 72 h following CPB. Ten received HSD immediately prior to CPB. All patients survived and were maintained in stable hemodynamic and metabolic condition throughout the study period. HSD induced high cardiac output, low vascular resistance immediately after administration. Vascular resistance remained low until the end of CPB. HSD patients ran a slightly negative fluid balance, while control patients ran a large positive fluid balance. HSD pretreatment is now used routinely for Jehovah's Witnesses undergoing CPB in our facility.