In this study, we introduce a new method for amide proton transfer imaging based on chemical exchange rotation transfer. It avoids several artifacts that plague conventional chemical exchange saturation transfer approaches by creating label and reference scans based on varying the irradiation pulse rotation angle (π and 2π radians) instead of the frequency offset (3.5 and −3.5 ppm). Specifically, conventional analysis is sensitive to confounding contributions from magnetic field (B0) inhomogeneities and, more problematically, inherently asymmetric macromolecular resonances. In addition, the lipid resonance at −3.5 ppm complicates the interpretation of the reference scan and decreases the resulting contrast. Finally, partial overlap of the amide signal by nearby amines and hydroxyls obscure the results. By avoiding these issues, our new method is a promising approach for imaging endogenous protein and peptide content and mapping pH. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.