Sufficient intravascular fluid therapy is of major importance in the treatment of the critically ill patient. The present study assessed whether the cardiorespiratory response of long-term volume replacement with low-molecular weight (LMW) hydroxyethyl starch solution (HES) differs from that of human albumin (HA). According to a randomized sequence, 30 trauma patients (injury severity score [ISS] between 15 and 30) and 30 sepsis patients (secondary to major general surgery) received either 10% HES (mean molecular weight 200,000 daltons; HES trauma [n = 15], HES sepsis [n = 15]) or human albumin 20% (HA trauma [n = 15], HA sepsis [n = 15]) over 5 days to keep pulmonary capillary wedge pressure (PCWP) between 12 and 18 mm Hg. Cardiorespiratory variables were measured by a pulmonary artery catheter on the day of inclusion into the study and daily during the next 5 days. Gastric intramucosal pH (pHi) was measured by tonometry. Central venous pressure and PCWP were comparable within the subgroups (trauma/sepsis) throughout the entire study period. In the trauma patients, cardiac index (CI), oxygen consumption index (VO2I), and oxygen delivery index (DO2I), significantly increased only in the HES-treated patients. In the sepsis patients, CI, VO2I, and DO2I increased and remained higher than baseline only in the HES group (P < 0.01). Right ventricular ejection fraction (RVEF) was reduced (< 40%) in the HA patients and increased only in the HES patients (from 34% +/- 4% to 42% +/- 3%; P < 0.05). pHi remained normal (> 7.35) in both trauma groups and in the HES-treated sepsis patients. In the HA sepsis group, pH, decreased (> 7.20) within the study period (7.15 +/- 0.12 on Day 4), indicating deteriorated splanchnic perfusion. We conclude that long-term intravascular fluid therapy with HA in traumatized and sepsis patients has no advantages in comparison to LMW-HES. In both groups, volume replacement with HES even resulted in improved systemic hemodynamics. Decrease in pHi in the sepsis patients was blunted by HES infusion indicating improved splanchnic perfusion by this regimen of volume therapy.