The proton relaxation rate enhancements produced by two types of iron oxide particles, M4125 and AM125 (Advanced Magnetics, Cambridge, MA) designed as potential MR contrast agents, have been measured in polyacrylamide gels and in liver and spleen. The organ uptakes, time courses, and biodistributions of these materials have been measured using radiolabeling. The relaxation rate enhancements produced by these particles have been related to the concentration of iron per gram material at different magnetic field strengths. The relaxation rates increase linearly as a function of concentration at field strengths varying from 0.15 to 7 T. The relaxation effects of these particles in tissue are significantly different from the behavior in vitro. These results suggest that several different mechanisms contribute to relaxation effects in the presence of iron oxide particles and they depend strongly on the way the particles are sequestered. Diffusion effects for a specified TE may be enhanced using gradient or single-spin echoes rather than multiple echoes. AM125 is significantly more effective as a relaxation agent than paramagnetic metal ions only at relatively high fields, while M4125 is less effective per unit concentration.