In an attempt to find better ways to treat myositis, the group has explored the use of both established medications used in new ways or combinations or new therapies. These trials are virtually the only such trials of the treatment of this very uncommon condition and thus also serve to draw patients to the Clinical Center for the other research projects carried out by the group on the basic mechanisms of myositis and related or mimicking diseases (outlined in ZO1 AR 41074-08 and ZO1 AR 41099-03). A randomized, crossover trial of high dose intravenous methotrexate with leucovorin rescue and of a combination of oral methotrexate and azathioprine has been completed in the past year and an analysis of the results is being prepared for publication. We have begun a trial of the purine analogue, fludarabine, in the therapy of myositis. A quantitative method of assessing muscle inflammation in myositis has been developed and will be used in current and future therapeutic trials. Thirteen of the planned sixteen patients have entered the trial so far, of whom almost half have completed the six-month treatment phase. A trial of the anti-thyroid drug, methimazole, will be begun in the next year. This agent was chosen because it may alter the ability of muscle cells to serve as a target for immunologic attack. In this past year, the methods for assessing the effect of the drug on muscle and blood cells have been developed in collaboration with NIDDK & NCI.