Leiden University Hospital is the national referral center for the management of fetal isoimmunization in The Netherlands. In this observational study, blood gas and acid-base measurements from 286 pretransfusion samples and 214 paired posttransfusion samples of 113 fetuses were analyzed. In umbilical arterial blood, we found a significant positive correlation between the degree of anemia and pH, as well as a significant negative correlation between degree of anemia and pO2. However, umbilical venous blood gas and pH remained virtually unchanged even in severe anemia. During intrauterine transfusion with unbuffered adult red cells, there was a small but statistically significant decrease of pH and pO2 in fetal blood. We conclude that severe fetal anemia is associated with decreased umbilical arterial pH, but that umbilical venous pH remains normal until shortly before death.