OBJECTIVE: The purpose of this article is to study the effect of the administration of multiple IV doses of gadolinium-based contrast agent on the intrinsic T1 hyperintensity in the dentate nucleus and globus pallidus in patients with multiple sclerosis (MS). MATERIALS AND METHODS: A retrospective review of imaging in patients with relapsing-remitting MS was performed. Images of 20 patients who received four or more doses of gadolinium-based contrast agent were reviewed. Patients received the linear agent gadopentetate dimeglumine before 2011 and the macrocyclic agent gadobutrol from 2011 onward. Dentate nucleus-to-pons and globus pallidus-to-thalamus signal intensity (SI) ratios were evaluated. SI ratios were compared over time with multiple injections of gadolinium. Similar SI ratios were evaluated for six patients who received gadopentetate dimeglumine and then underwent multiple subsequent MRI studies without contrast agent administration. RESULTS: The increase in the dentate nucleus-to-pons SI ratio after multiple administrations of the linear agent gadopentetate dimeglumine (mean = 1.44; SD = 2.50) was significantly higher than that with the macrocyclic agent gadobutrol (mean = -0.11; SD = 2.33) (p < 0.001). The globus pallidus-to-thalamus and dentate nucleus-to-CSF ratios also increased with multiple contrast injections over time, but the changes were not found to be statistically significant. The increase in SI in the dentate nucleus was not observed in patients who stopped receiving contrast injections, after showing a previous increase over time with gadolinium. CONCLUSION: In patients with MS, SI within the dentate nucleus and globus pallidus increased on unenhanced T1-weighted images and was significantly greater with the administration of a linear agent than with a macrocyclic agent. This increase in SI over time is likely a reflection of gadolinium deposition and not due to intrinsic disease, as previously postulated.