Abstract: Methods are providing for characterizing multiple sclerosis disease activity in a subject. In the subject methods, a sample is obtained from a subject suspected of having or known to have multiple sclerosis. The sample is then assayed for the presence of both high and low molecular proteins having RNAse L activity and a ratio of these two proteins is derived. The resultant ratio is then used to characterize the MS disease activity in the subject, e.g. to confirm an initial MS diagnosis, to determine the stage of the disease, to monitor disease progression, to predict disease attacks, and the like. Also provided by the subject invention are kits for practicing the methods.