Electrospray ionization spectra of positive multiply charged ions of several proteins with molecular weight from 8565 to 339,100 u were recorded at different pressures of residual gas in the vacuum chamber of an electrospray time-of-flight mass spectrometer. The pressure was varied in the range (0.2 to 5) × 10(-6) torr. The effect of pressure was found to be significant even for the lightest protein investigated (ubiquitin), which resulted in a decrease of both sensitivity and resolution. Investigations of the arrival-time distributions and the energy distributions of ions showed that collision-induced dissociation (CID) of the protein ions in the drift region is the main process responsible for the effect. Several CID cross sections of proteins were estimated from a series of mass spectra recorded at different pressures in the reflecting mode: 1150 Å(2) for cytochrome c (averaged over charge states z = 14-18), 800 Å(2) for lysozyme (z = 8-10), 1840 Å(2) for apomyoglobin (z = 12-25), 800 Å(2) for holomyoglobin (z = 8), and 2500 Å(2) for carbonic anhydrase II (z = 22-35). Several experiments with large proteins in their native conformations and low charge states (m/z 0,000) demonstrate that these ions are less sensitive to high residual gas pressure.