Human fetal umbilical venous pressure was measured during 20 intravascular transfusions performed for treatment of hemolytic anemia. The mean (+/- 1 SEM) gestational age at the time of transfusion was 29.3 +/- 1 weeks and the mean beginning hematocrit was 27% +/- 2%. The mean volume of infused packed red blood cells (70% hematocrit) was 90.3 +/- 7 ml. The mean hematocrit at completion of the procedure was 48% +/- 1%. In nonhydropic fetuses umbilical venous pressure rose progressively from 6.7 +/- 1 mm Hg at the start of transfusion to 10.9 +/- 1 mm Hg at the completion of transfusion (p less than 0.002). However, most fetuses who began the infusion with a normal umbilical venous pressure ended the transfusion with a normal umbilical venous pressure (less than 10 mm Hg). Fetuses with immune hydrops (n = 2) had elevated umbilical venous pressure values before the initiation of transfusion therapy when compared with the first transfusion of nonhydropic fetuses (12.5 +/- 0.5 vs. 5.7 +/- 1 mm Hg, p = 0.01). However, the umbilical venous pressure measurements declined into the normal range within 24 hours of the first transfusion; this normalization was too rapid to be explained by the reversal of liver hypertrophy or portal hypertension. There was no demonstrable relationship between the rise in umbilical venous pressure and either the gestational age, the volume transfused, or the rise in hematocrit. This study demonstrated: (1) In terms of the umbilical venous pressure, direct intravenous infusion of the human anemic fetus is well tolerated; (2) the elevated umbilical venous pressure associated with immune hydrops can correct rapidly with red blood cell replacement.