We have previously shown that both plasma protein restitution and plasma volume restitution are significantly enhanced in female rats hemorrhaged during the proestrus phase of the estrous cycle. Estradiol and progesterone levels are markedly elevated during proestrus, and also increase during pregnancy. The present studies were therefore designed to determine if the ability to restore plasma protein and blood volume after hemorrhage is augmented during pregnancy, and by chronically elevated estradiol levels. The response to moderate hemorrhage (22-23% blood loss) was evaluated in conscious pregnant rats during early and mid-gestation, and compared with that of virgin female rats studied during metestrus. At 22 hrs post-hemorrhage, plasma volume had increased to greater than basal levels, and blood volume was restored to 93±1% (metestrus), 91±2% (early pregnancy) and 98±2% (mid-gestation) of control (P>0.05). Animals hemorrhaged during metestrus or early pregnancy restored the same amount of protein to the plasma as had been removed, whereas those hemorrhaged during mid-gestation restored nearly 50% more plasma protein than had been removed (P<0.01). In ovariectomized animals with chronic steroid replacement that maintained plasma progesterone at metestrus levels (15±2 ng/ml), but raised plasma estradiol to 2-fold that of mid-gestation (22±3 pg/ml), the blood volume and plasma protein restitution responses to hemorrhage did not differ from those of ovariectomized animals with no steroid replacement. In summary, post-hemorrhage restoration of plasma protein content is significantly augmented during mid-gestation, but not during early pregnancy. This augmented response cannot be attributed to chronic elevation of plasma estradiol levels alone.