The aim of this study was to investigate whether the type of i.v. fluid administered has an impact on outcome in an animal model of septic shock. The study included 28 anesthetized, invasively monitored, mechanically ventilated female sheep (29.5 ± 4.0 kg), which received 0.5 g/kg body weight of feces into the abdominal cavity to induce peritonitis. During the surgical operation and 4 h after feces spillage, only Ringer's lactate (RL) was administered in all animals. Thereafter, animals were randomized to receive continuous infusions of RL (n = 7) alone or combined with either 20% albumin (n = 7, volume ratio to RL 1:10) or 6% hydroxyethyl starch (HES) (n = 7, volume ratio to RL 1:1), or gelatin alone (n= 7, no volume limitation). Fluid resuscitation was titrated to maintain pulmonary artery occlusion pressure at baseline levels throughout the experiment. No antibiotics or vasoactive drugs were administered, and animals were monitored until their spontaneous death. Hemodynamic variables were better with HES and albumin than with the other fluids, as reflected by higher stroke volume, cardiac index, and oxygen delivery (all P < 0.05). Hydroxyethyl-starch-treated animals also had lower arterial lactate concentrations (P < 0.01). However, times to develop hypotension and oliguria were similar in all groups. Blood interleukin (IL) 6 concentrations were significantly increased in all groups. The mean survival time was similar in all groups. In this clinically relevant model of prolonged septic shock, albumin and HES solution resulted in higher cardiac output, oxygen delivery, and lower blood lactate levels than gelatin and RL; however, the choice of i.v. fluid did not affect outcome.