RATIONALE AND OBJECTIVES. The authors studied the long-term distribution of gadolinium (Gd) in mice and rats after the administration of four commercially available magnetic resonance imaging contrast media. The goals were to determine any possible product dissociation in vivo and to evaluate the effects that product excipients had on the tissue distributions. METHODS. Gadolinium-153 (Gd-153)-labeled gadopentetate (Magnevist), gadoteridol (ProHance), gadoterate (Dotarem), and gadodiamide (Omniscan) were administered intravenously to mice (0.48 mmol/kg) and rats (0.1 mmol/kg), At various times up to 14 days posttreatment, the residual Gd-153 VIIS measured in selected tissues, The tissue distributions obtained were used to make intra- and interchelate distribution evaluations and comparisons regarding tissue clearance and any possible in vivo dissociation of the Gd chelates. RESULTS. Differences were found among the chelates studied relative to the amounts of residual Gd-153 present in tissues known to sequester free Gd, particularly in liver and femur at 7 and 14 days after administration, in both mice and rats, The pattern of the Gd-153 distribution suggested that the linear chelates, gadopentetate and gadodiamide, dissociated in vivo resulting in more Gd-153 present in bone and liver at the longer residence times than in the subjects injected with the macrocyclic chelates, gadoteridol and gadoterate, The only excipient found to affect the distribution profile was calcium(DTPA-BMA): this excipient in formulated gadodiamide decreased the amounts of residual Gd measured in whole body, bone, and liver in mice compared with levels obtained when gadodiamide was injected alone. CONCLUSIONS. The molecular feature found to he most important in differentiating the four chelates evaluated is the presence or absence of a macrocyclic structure, The Gd chelates containing this structure, gadoteridol and gadoterate, have the lowest residual Gd at long residence times in both mice and rats, The order of residual whole body Gd at 14 days (lowest to highest) was: gadoteridol similar to gadoterate less than or equal to gadopentetate '' gadodiamide, The only excipient that affected the biodistribution,vas found in the gadodiamide formulation where the addition of 5% calcium (DTPA-BMA) reduced residual Gd to just less than 10 times greater than that found for the macrocyclic chelates with the lowest residual Gd, gadoteridol and gadoterate.