To retrospectively document hyperintense lesions on nonenhanced T1-weighted magnetic resonance (MR) images in patients with multiple sclerosis (MS) and study their relationship to physical disability, disease course, and other MR markers of tissue damage (brain atrophy). Institutional review board approval was obtained; informed consent was waived for this HIPAA-compliant study, with 145 patients with MS (mean age, 43 years). Patients had relapsing-remitting (RR) (n=92) or secondary-progressive (SP) (n=49) MS; clinical course was unknown in four. Mean Expanded Disability Status Scale (EDSS) score was 3.5. T1 lesions were compared with normal white matter on nonenhanced images and judged hyperintense. Spearman rank correlation, Wilcoxon rank sum, and Fisher exact probability tests and analysis of variance and analysis of covariance (ANCOVA) were employed. At least one T1 hyperintense lesion was found in 113 patients (total, 340 lesions). Two-thirds of lesions had hyperintense rim; others were uniformly hyperintense. Lesions were more common in patients with SP MS (P=.003, Wilcoxon test) and correlated with EDSS score (Spearman rho=0.19, P=.04) and brain atrophy measures (total cortical atrophy, Spearman rho=0.42, P<.001; third ventricular width, Spearman rho=0.40, P<.001) but not disease duration (Spearman rho=0.038, P=.69). Lesions were more likely multiple in the SP versus RR group (P<.001, Fisher test). After adjustment for disease course, T1 hyperintense lesions remained associated with brain atrophy (P<or=.001, ANCOVA). No independent effect of imager type (ANCOVA F value=1.4, P=.24) or spin-echo method (P=.67, Wilcoxon test) on number of lesions was detected. An effect of other MR protocol adjustments (analysis of variance F value=5.6, P=.001) was unconfirmed after clinical characteristic adjustment (ANCOVA F value=1.1, P=.35). Hyperintense MS plaques on T1-weighted MR images are common and associated with brain atrophy, disability, and advancing disease; a hyperintense lesion may be a clinically relevant biomarker.