The concentrations of serum albumin and albumin reserve for bilirubin binding were studied in 24 healthy women during and after pregnancy, using monoacetyl-4,4'-diaminodiphenylsulphone as a deputy ligand for bilirubin. In the first trimester, the serum albumin concentration was already diminished. Likewise, the serum reserve albumin for bilirubin binding was reduced gradually during pregnancy. These reductions were evident as early as the 20th week of gestation, and at delivery the level averaged 53% of the nonpregnant level. The reduction in bilirubin binding capacity was partly dependent on the decreasing serum albumin concentration, but a reduction in the albumin molecule's binding capability was also shown. This binding defect, which is also present in neonates, is not fully explained. The reduction in bilirubin binding capability probably reflects a reduced degree of protein binding for many protein-bound drugs during pregnancy, which may contribute to pharmacokinetic alterations in pregnancy