In this study, we analyzed the proteins in plasma of workers exposed to benzene by two-dimensional gel electrophoresis, in the hope of finding a specific protein suitable for the biomonitoring of benzene exposure. Comet assays were also carried out to evaluate lymphocytes DNA damage. Fifty workers from a printing company and 38 matched unexposed healthy subjects were enrolled in the study. DNA damage was found to be significantly higher in the exposed workers than in the controls. The tail moments of the two groups were 2.07 +/- 0.35 and 1.48 +/- 0.41, respectively (P < 0.0001). The mean values of trans, trans-muconic acid (t,t-MA) in workers exposed to benzene and in unexposed subjects were 1.011 +/- 0.249 and 0.026 +/- 0.028 mg/g creatinine, respectively. Protein profiles were significantly different (P < 0.05) in the two groups, as identified by matrix-assisted laser desorption ionization/time of flight (MALDI-TOF) mass spectrometry and confirmed by Western blot. T cell receptor beta chain (TCR beta), FK506-binding protein (FKBP51) and matrix metalloproteinase-13 (MMP13) were found to be up-regulated in the benzene-exposed workers. In addition, the correlation between TCR beta and the tail moments of lymphocytes was statistically significant (r-value, 0.428). We conclude that TCR beta in plasma could be used for the early detection of exposure to benzene.