Hypertonic saline solution appears to be an attractive method of volume expansion. In 45 patients undergoing elective aorto-coronary bypass grafting, endocrinologic and circulatory responses to volume loading with hypertonic saline solution prepared in low molecular weight (MW) hydroxyethyl starch (HES) solution (72 g/L NaCl, HES concentration: 6%; MW: 200,000 D; degree of substitution [DS]: 0.5) (HS-HES) was compared randomly to patients who had received low molecular weight HES solution (LMW-HES). A group of patients without volume loading served as a control. Volume was infused to double the low pulmonary capillary wedge pressure (PCWP < 5 mmHg) after induction of anesthesia. Plasma levels of atrial natriuretic peptide (ANP), endothelin, vasopressin, and catecholamines were measured before, during, and after cardiopulmonary bypass (CPB) until the first postoperative day. In addition to systemic circulatory changes, capillary skin blood flow was measured by laser Doppler flowmetry. ANP plasma concentration increased in both volume groups (HS-HES: +79%; HES: +32%), whereas it decreased in the control (-20%). Infusion of HS-HES resulted in an increase in plasma endothelin concentration before and after CPB (from 3 to 6 pg/mL). Five hours after CPB, both treatment groups had higher endothelin plasma concentrations than the control patients (P < 0.05). Epinephrine and norepinephrine plasma levels increased most markedly in the control patients and were highest in the postbypass period in these patients. CI increased most after infusion of HS-HES (+65%) (P < 0.05). In the postbypass period, CI remained significantly higher in both volume groups than in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)