A model of MRI signal intensity was developed for chromatography column phantoms containing Sephadex gels, which were used to simulate tissue perfusion and the exchange of protons between extravascular and intravascular tissue compartments. Computer simulations of two-compartment and three-compartment models were compared in experiments that used two chromatography columns. One column contained a Sephadex G-25 gel that had a smaller pore size and a slower rate of exchange between extrabead and intrabead compartments than did a second column, which contained a G-50 gel with a larger pore size. In both columns the beads were of approximately the same size to simulate the same ratio of intrabead volume to extrabead volume. Slice-selective spin-echo experiments were performed with the columns oriented parallel to each other in a 1.5 T imager and parallel to the magnetic field, with water flowing through each column perpendicular to the slice at mean flow velocities ranging between 0 and 0.66 mm/s. The results of the experiments agreed with computer simulations, which showed that the MRI signal intensity in the perfused columns is a function of the rate of exchange between extrabead and intrabead compartments. The exchange process modifies the transit time of protons passing through an excited region. The simulations also showed that both two-compartment and three-compartment models could be used to fit the experimental data. Experiments with chromatography gel columns are a preliminary investigation into the potential of using MRI to measure the exchange between extravascular and intravascular compartments of endogenous protons during blood perfusion of biological tissue.