The comparative in vitro metabolism of the flame retardant tetrabromo-bisphenol A was studied in rat and human using a [(14)C]-radio-labelled molecule. Tetrabromo-bisphenol A is metabolised into the corresponding glucuronide (liver S9 fractions) and several other metabolites produced by cytochrome P450 dependent pathways (liver microsomes and liver S9 fractions). No major qualitative differences were observed between rat and human, regardless of the selected concentration, within the 20-200 microM range. Tetrabromo-bisphenol A undergoes an oxidative cleavage near the central carbon of the molecule, that leads to the production of hydroxylated dibromo-phenol, hydroxylated dibromo-isopropyl-phenol and glutathione conjugated dibromo-isopropyl-phenol. The main metabolites of tetrabromo-bisphenol A are two molecules of lower polarity than the parent compound, characterised as a hexa-brominated compound with three aromatic rings and a hepta-brominated dimer-like compound, respectively. Both structures, as well as the lower molecular weight metabolites resulting from the breakdown of the molecule, suggest the occurrence of chemically reactive intermediates formed following a first step oxidation of tetrabromo-bisphenol A.