A complete set of phenomenologically based analytical expressions, using a modified Bloch formalism, incorporating both off-resonance-irradiation and magnetization-transfer effects, was derived to represent the theoretical response of the water and macromolecular protons in tissue to off-resonance proton irradiation. This treatment was shown to be identical to that obtained by the extension of the formalism for rotating-frame spin-lattice relaxation in the presence of an off-resonance-irradiation field which included the effects of cross relaxation. Computer simulations are presented illustrating the steady-state behavior of both the water and the macromolecular protons magnetically coupled by cross relaxation, in an off-resonance proton-irradiation experiment. The analytical expressions obtained were used to analyze the response of water protons in rat-muscle tissue to off-resonance proton irradiation. Very good agreement between the experimental and expected theoretical intensity-ratio dispersion behaviors for water protons was observed. Furthermore, for this tissue the dispersive behavior of the water-proton intensity ratio does not faithfully reflect the response of the macromolecular protons, as would be expected if the cross-relaxation-rate constant for magnetization transfer was much greater than the intrinsic rate constant for longitudinal relaxation of the bulk-water protons. Unambiguous analysis of the dispersion behavior of tissue water protons using the phenomenologically based analytical expressions derived in this study required magnetic-resonance parameters obtained from ancillary magnetic-resonance experiments. © 1991.