Protein expression in foetal brain with or without chromosome 21 trisomy (Down's syndrome) was analyzed by two-dimensional gel electrophoresis and mass spectrometry. Data generated by in-gel digestion and matrix-assisted laser desorption/ionization mass spectrometry allowed identification of 40 proteins. Most of these are common to syndrome and healthy subjects and represent different types of protein. However, a few proteins, identified as truncated structural proteins (tubulin, actin), were present in part of the trisomy samples but absent from the controls. This is interpreted to indicate increased proteolysis in the syndrome samples but could also reflect some altered expression or processing. Independent of the apparently increased proteolysis in the syndrome samples, and in spite of the use of total brain tissues, the results show that two-dimensional protein separation patterns are largely similar between the syndrome and control samples upon silver-staining, but that differences associated with structural components can be detected and identified.