2-D Difference gel electrophoresis (DIGE) circumvents many of the problems associated with gel comparison via the traditional 2-DE approach. DIGE's accuracy and precision, however, is compromised by the existence of other significant sources of systematic variation, including that caused by the apparatus used for imaging proteins (location of the camera and lighting units, background material, imperfections within that material, etc.). Through a series of experiments, we estimate some of these factors, and account for their effect on the DIGE experimental data, thus providing improved estimates of the true relative protein intensities. The model presented here includes 2-DE images as a special case.