The construction of two ultrafiltration devices which, under application of high-pressure liquid chromatographic (HPLC) technique, allow the determination of unbound portions of drugs in albumin solutions is described. The usefulness of this method and its advantages compared with prevailing methods are demonstrated by means of determination of the unbound portion of carbamazepine, chlorpromazine, phenobarbital and phenprocoumon in buffered bovine serum albumin solutions (4%). The binding of each drug to albumin was characterised by determining the overall binding constant (K1), the apparent binding constant (k+), the free reaction energy (delta F0), the number of binding sites per albumin molecule (n), the rate of taking up of drug by albumin (V) and the unbound portions of the drug (alpha).