The human whole saliva proteome was investigated using two-dimensional liquid chromatography (2-DLC). The 2-DLC study was able to identify, with high confidence, 102 proteins including most known salivary proteins (35), and a large number of common serum proteins (67). Peptides from proline-rich proteins, abundant in saliva, had unusual cleavage sites and were frequently only partially tryptic. Three proteins not previously observed in human saliva were also detected. Significantly greater numbers of identified proteins, including high molecular weight, low molecular weight, and proline-rich proteins, were found with 2-DLC compared to previously reported two-dimensional gel electrophoresis studies.