Cell-free hemoglobin solutions can scavenge nitric oxide and therefore increase mean arterial pressure (MAP). The present study investigated the effects of a continuous low-dose infusion of modified hemoglobin during ovine hyperdynamic sepsis. 13 sheep received a continuous infusion of live Pseudomonas aeruginosa bacteria for 48 h. Animals that survived the first 24 h of sepsis (n=12) were randomly assigned either to a treatment group that received 20 mg x kg(-1) x h(-1) pyridoxalated hemoglobin polyoxyethylene conjugate (PHP) for 20 h or to a control group that received the same volume of the vehicle for 20 h. MAP increased in the treatment group during 4 h of PHP infusion 12.7+/-1.7 mmHg (p < .05) and after 20 h of PHP infusion MAP was still 12.4+/-2.1 mmHg above the MAP before starting PHP (p < .05). MAP in the control group did not change significantly from 24 h to 48 h of sepsis. No differences in regional blood flow were seen between groups. Bacterial counts in the spleen and kidney were lower in the treatment group than in the control group. Continuous low-dose infusion of PHP can normalize systemic vascular resistance and MAP for long periods without deterioration of regional blood flow or bacterial clearance.