Desalted plasma from a 2,4- and 2,6-toluene diisocyanate (2,4- and 2,6-TDI) exposed worker at a factory producing flexible polyurethane foam was separated and fractionated into 200 fractions using ion-exchange chromatography followed by a gel-filtration separation and fractionation into 59 fractions. The corresponding amines (to the isocyanates), 2,4- and 2,6-toluenediamine (2,4- and 2,6-TDA), were determined in each fraction after sulfuric acid hydrolysis as pentafluoropropionic anhydride derivatives by capillary gas chromatography and chemical ionisation mass spectrometry monitoring negative ions. The ion exchange fractions containing TDA (81-115) were added together and the solution was separated and fractionated on the gel-filtration column. The fractions 81-115 contained 84 and 72% of 2,4- and 2,6-TDA, respectively, as compared to the unfractionated plasma. The gel filtration fractions 22-27 contained 107 and 119% of 2,4- and 2,6-TDA, respectively, as compared to the amounts in the ion exchange fractions (81-115). Agarose gel-electrophoresis and electroimmunoassay demonstrated that albumin, 2,4- and 2,6-TDA co-eluted in both ion-exchange and gel-filtration chromatography. Quantitative determination of albumin, 2,4- and 2,6-TDA also demonstrated that these components co-eluted using albumin-immunosorption chromatography. In addition, studies of affinity isolated IgG revealed that this fraction was devoid of 2,4- and 2,6-TDA. These results indicate that albumin is the major receptor molecule for 2,4- and 2,6-TDI in blood plasma and that these isocyanates form covalent bondings with albumin.