Human saliva performs a wide variety of biological functions that are critical for the maintenance of the oral health. Various functions include lubrication, buffering, antimicrobial protection, and the maintenance of mucosal integrity. In addition, whole saliva may be analysed for the diagnosis of human systemic diseases, since it can be readily collected and contains identifiable serum constituents. By using proteomic approach, we have established a reference proteome map of human whole saliva allowing for the resolution of greater than 200 protein spots in a single two-dimensional polyacrylamide gel. Fifty-four protein spots, comprised of 26 different proteins, were identifies using N-terminal sequencing, mass spectrometry, and/or computer matching with protein database. Ten proteins, whose levels were significantly different when bleeding had occurred in the oral cavity, were discussed in this study. These 10 proteins include alpha-1-antrypsin, apolipoprotein A-I, cystatin A, SA, SA-III, and SN, enolase I, hemoglobin beta-chain, thioredoxin peroxiredoxin B, as well as a prolactin-inducible protein. The proteomic approach identifies candidates from human whole saliva that may prove to be of diagnostic and therapeutic significance.