There is an ongoing need to evaluate the impact of various digital image processing and display variables on diagnostic image quality. In most cases, evaluation includes comparison of images, often multiple versions of the same image. In order to improve speed and sensitivity, new protocols were developed to enhance a radiologist's ability to detect subtle changes in images and provide a means to quantify differences in a standard fashion. The protocols make use of the rapid sequential display of registered images on a single high- resolution CRT (a.k.a., flicker) and 2X magnification in order to increase observer sensitivity. The flicker technique was implemented in the form of an image comparison workstation (ICW) that was designed to facilitate the evaluation of different image processing options. The ICW was developed with capabilities to interactively control the rate of flicker between image pairs (up to 5 Hz), the degree of image magnification (1X to 4X), and the selection of the region of interest (ROI). Three specific protocols were developed based on the flicker technique, two forms of forced-choice and a rank-ordering protocol employing a reference set comprised of images with varying degrees of spatial-resolution degradation. All three protocols were exercised as part of an observe study whose goal was to establish visually lossless compression levels for JPEG and a wavelet-transform based algorithm. The results indicate that, for high resolution digitally acquired posteroanterior (PA) chest radiographs presented to observers at 2X magnification on a 2K X 2.5K addressable pixel monochrome display, the visually lossless thresholds for both JPEG and wavelet occur in the range of 2.0 to 1.5 bits-per- pixel (approximately equals 10:1). These results are a conservative estimate of the visually lossless threshold because of the sensitive nature of the experimental methodology.