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The success of colchicine therapy in the management of familial Mediterranean fever has provided new direction to investigations into the pathogenesis of this disease. Examination of HLA antigen frequencies in 53 patients with familial Mediterranean fever and appropriate controls, as well as various immunologic studies have yielded no significant differences. However, B lymphocyte typing and assays for immune complexes, lymphokines and prostaglandins may be of potential interest. Preliminary studies indicate that leukocytes of patients with familial Mediterranean fever release increased amounts of lysozyme (P<0.01), when subjected to high temperatures, and of both lysozyme and myeloperoxidase at low osmotic concentrations. The known and potential effects of colchicine on leukocyte and cellular metabolism, and the current status of colchicine prophylaxis are reviewed. In patients receiving an optimum colchicine dose of 1.5 to 1.8 mg per day, side effects have been minimal and the frequency of attacks has been decreased significantly.