Purpose: To perform T1 measurements using inversion recovery (IR) echoplanar imaging (EPI) to evaluate reproducibility, normal values, and T1 histogram analysis as a measure of disease progression in multiple sclerosis (MS) patients. Materials and Methods: Multislice IR-EPI was performed in 10 controls and 36 MS patients. Region-of-interest (ROI) and T 1 histogram analysis were performed on T1 maps and compared to hypointense T1 lesions and brain atrophy in MS patients. Results: Coefficient of variation (COV) varied from 1.6% to 4.9%. Callosal normal (appearing) white matter (N(A)WM) showed the lowest and cortical gray matter the highest T1 values. T1 histogram analysis in controls showed a sharp WM peak centered on a T1 value of 729 msec (range = 679-765) with extension into a shoulder of higher T1 values. In MS patients, a shift toward higher T1 values (mean = 788 msec, range = 700-957) with a lower relative peak amplitude was present, predominantly resulting from T1 prolongation in NAWM. T1 histogram parameters strongly related to hypointense T1 lesion volume and brain atrophy in MS patients. Conclusions: IR-EPI provides a reproducible method to obtain T1 values in the brain. Regional variation in T1 values is present in N(A)WM of volunteers and MS patients. Since T1 histogram parameters reflect changes in NAWM and correlate with conventional measures of disease burden in MS patients, T 1 histogram analysis may provide a global measure of disease progression in MS.