We tested the hypothesis that a decrease in the blood-to-tissue movement of albumin contributes to the recovery of plasma albumin and plasma volume after acute plasma protein depletion (plasmapheresis). Awake and unrestrained male Sprague-Dawley rats (220-320 g) fitted with jugular catheters were plasmapheresed, and plasma volume, plasma albumin, and total plasma protein content were measured at 1, 5, 24, and 48 h postplasmapheresis. Plasma volume recovered to baseline within 1 h (4.6 +/- 0.42 vs. 4.7 +/- 0.46 mL/100 g body weight (bw), remained at baseline from 5 h to 24 h but increased to 5.5 + 0.57 mL/100 g bw at 48 h (P < 0.05). Plasma albumin and total protein content recovered rapidly but remained below baseline levels at 1 h (10.05 +/- 0.98 vs. 12.33 +/- 1.29 and 19.75 +/- 1.75 vs. 24.73 +/- 2.56 mg/100 g bw, respectively). Plasma protein content retumed to baseline by 5 h of recovery. Tissue uptake of I125-labeled albumin decreased in the heart, skin, skeletal muscle, and small Intestines of plasmapheresed rats (P < 0.05). These data support the hypothesis that a reduction in albumin efflux from the vascular space contrlbutes to the recovery of plasma albumin and total protein content during plasma volume recovery and eventual expansion after plasmapheresis.