The objective of this study was to investigate the fate of TDI in biological matrices due to its chemical reactivity. The chemistry and biochemistry of isocyanate compounds have been reviewed (Brown, 1986; Brown and Kennedy, 1989). However, as yet, a systematic investigation is not available on the quantitative, qualitative and kinetic aspects of the reactivity of these compounds in biological matrices such as aqueous buffer solutions, protein model systems, blood, plasma, urine and stomach contents. A limited study was performed to analyze the in vitro reactivity of the 2,6 isomer of TDrin fluids such as stomach contents and sera (Jeffcoat, 1985). In both fluids, the half-life of the 2,6 TDI was 2 minutes or less and the reactivity was dependent on the delivering solvent. This data has been extended through a systematic investigation of each of the individual isomers of TDI and of the commercial 80/20 2,4/2,6-TDI isomer mixture. It is also important to address not only the loss of reactive isocyanate but also the fate of the reactive compound. Detailed knowledge of the specificity and kinetics of the reactivity of these compounds under aqueous conditions will help to define the behavior of TDI in animal and man.