An MRI technique is proposed for complete fat signal elimination. This approach exploits the fact that water rapidly exchanges magnetization with protons in protein and membrane phospholipid of tissue and cells but does not exchange magnetization with triglyceride or fat protons in the tissue. Saturation of the proton signal from protein and membrane phospholipid thus results in partial saturation of the water proton signal, allowing acquisition of an image including a portion of the water signal and the full fat signal. Subtraction of this image from the standard image, containing both water and fat signals, results in an image in which all fat signal is cancelled. This fat-free image is sensitive to magnetization transfer and to water density and relaxation time, providing the possibility of additional contrast. Unlike most fat suppression techniques, this method is not compromised by the static or radiofrequency field heterogeneity and is equally efficient for all fat resonances independent of their chemical shift frequency. Magn Reson Med, 2010. © 2010 Wiley-Liss, Inc.