Measurement of blood volume (BV) may guide fluid and red blood cell management in critically ill patients when capillary leak from shock and fluid resuscitation makes assessment of intravascular volume difficult. This is a prospective randomized trial of critically ill surgical patients with septic shock, severe sepsis, severe respiratory failure, and/or cardiovascular collapse. The control group received fluid management based on pulmonary artery catheter parameters and red blood cell transfusions based on hematocrit values. The BV group received fluid and red blood cell transfusions based on BV analyses in addition to pulmonary artery catheter parameters. Blood volume was measured using the radioisotope tracer technique with iodine 131-labeled albumin. This allowed direct measurement of plasma volume and calculation of the red blood cell volume. The control group was blinded to the BV results. There were statistically significantly more times when the control group (compared with the BV group) demonstrated hypervolemia (48% vs. 37%) and red blood cell deficiency (33% vs. 16%). There was a delay in red blood cell transfusions administered to the control group by 1.5 +/- 2 days at which time the abnormality became clinically evident. Blood volume analyses provided additional information to the clinicians resulting in a change in treatment in 44% of the time to patients randomized to the BV group. The mortality rates were significantly different between the two groups (8% for the BV group and 24% in the control group; P = 0.03). Blood volume measurements allowed the physicians to promptly treat physiologic disturbances in both red blood cell volume and plasma volume, resulting in improved survival.