The pharmacokinetics and metabolic fate of the intrinsically active (anti-HIV) drug carrier succinylated human serum albumin (Suc-HSA) was studied in rats. Suc-HSA was prepared by derivatizing HSA with 1,4-[14C]-succinic anhydride, a modification by which all available epsilon NH2-groups in HSA were converted into carboxylic groups. After i.v. injections of 0.3, 1.0, 3.0 and 10.0 mg/kg in freely moving rats, Suc-HSA showed a dose dependent elimination pattern, indicating a saturable elimination pathway. The Michaelis-Menten parameters Vmax and Km were 98.7 micrograms.min-1.kg-1 and 8.5 micrograms.ml-1 respectively. The kinetics of Suc-HSA was influenced by anaesthesia. In anaesthetised animals, Vmax and Km were found to be 26.9 micrograms.min-1.kg-1 and 0.26 microgram.ml-1, respectively. This implies an intrinsic clearance of 100 ml.min-1.kg-1, which is about 10-fold higher as compared to 12 ml.min-1.kg-1 in freely moving animals. Intravenous administration of a sub-saturable dose of 3.0 mg.kg-1 1,4-[14C]-Suc-HSA to freely moving rats resulted in a biphasic elimination with an initial t 1/2 of 20 min and a terminal t 1/2 of 40 hrs. Excretion of metabolites in urine and faeces lasted for at least 48 hours. About 70% of the radioactive dose was excreted in urine, whereas maximally 2% was detected in faeces. Suc-HSA was degraded to its individual amino acids including succinylated lysine (the only radioactive product formed). Succinylated lysine was not further metabolised and mainly excreted via the urine. Immunohistochemical staining showed that even after 48 hrs Suc-HSA could be detected in livers. Together with the urinary excretion patterns, this points to a gradual degradation of Suc-HSA.