Purpose To determine whether repeated exposure of the pediatric brain to a linear gadolinium-based contrast agent (GBCA) is associated with an increase in signal intensity (SI) relative to that in GBCA-naive control subjects at unenhanced T1-weighted magnetic resonance (MR) imaging. Materials and Methods This single-center, retrospective study was approved by the institutional review board and compliant with HIPAA. The authors evaluated 46 pediatric patients who had undergone at least three GBCA-enhanced MR examinations (30 patients for two-group analysis and 16 for pre- and post-GBCA exposure comparisons) and 57 age-matched GBCA-naive control subjects. The SI in the globus pallidus, thalamus, dentate nucleus, and pons was measured at unenhanced T1-weighted MR imaging. Globus pallidus-thalamus and dentate nucleus-pons SI ratios were calculated and compared between groups and relative to total cumulative gadolinium dose, age, sex, and number of and mean time between GBCA-enhanced examinations. Analysis included the Wilcoxon signed rank test, Wilcoxon rank sum test, and Spearman correlation coefficient. Results Patients who underwent multiple GBCA-enhanced examinations had increased SI ratios within the dentate nucleus (mean SI ratio ± standard error of the mean for two-group comparison: 1.007 ± 0.0058 for GBCA-naive group and 1.046 ± 0.0060 for GBCA-exposed group [P < .001]; mean SI ratio for pre- and post-GBCA comparison: 0.995 ± 0.0062 for pre-GBCA group and 1.035 ± 0.0063 for post-GBCA group [P < .001]) but not the globus pallidus (mean SI ratio for two-group comparison: 1.131 ± 0.0070 for GBCA-naive group and 1.014 ± 0.0091 for GBCA-exposed group [P = .21]; mean SI ratio for pre- and post-GBCA comparison: 1.068 ± 0.0094 for pre-GBCA group and 1.093 ± 0.0134 for post-GBCA group [P = .12]). There was a significant correlation between dentate nucleus SI and total cumulative gadolinium dose (r = 0.4; 95% confidence interval [CI]: 0.03, 0.67; P = .03), but not between dentate nucleus SI and patient age (r = 0.23; 95% CI: -0.15, 0.56; P = .22), sex (mean SI ratio: 1.046 ± 0.0072 for boys and 1.045 ± 0.0110 for girls; P = .88), number of contrast-enhanced examinations (r = 0.13; 95% CI: -0.25, 0.48; P = .49), or time between contrast-enhanced examinations (r = -0.06; 95% CI: -0.42, 0.32; P = .75). Conclusion SI in the pediatric brain increases on unenhanced T1-weighted MR images with repeated exposure to a linear GBCA. © RSNA, 2016.