Break-through symptoms (BTS) in multiple sclerosis (MS) patients on beta-interferon (beta-IFN) monotherapy are most frequently treated with a brief administration of steroids. Here, we report the results of monitoring serum immunologic markers recorded at three-month intervals for 1.5 years in responders to beta-INF 1a (Avonex) monotherapy (n =21) and MS patients placed on Avonex with prednisone (n =83) and Avonex, prednisone and azathioprine (AZA) (n =21) because of BTS. Compared to 23 healthy controls, patients on Avonex monotherapy and Avonex with prednisone, in individuals on Avonex, prednisone and AZA, a significant decrease in serum concentration of soluble intercellular adhesion molecule-1 (sICAM-1) (P=0.001) was established. Combined therapy with Avonex, prednisone and AZA was associated with a significant increase in the serum level of interleukin (IL)10 (P <0.001). Compared to Avonex monotherapy, combined therapy suppressed the serum level of IL12p40, antagonized elevation in the serum concentration of soluble IL2 receptor (sIL2R) and inhibited an increase in the serum soluble CD95 (sCD95) molecule. In patients studied, no significant differences in the serum level of IL18 and tumor necrosis factor-alpha (TNF-alpha) were established. These findings are important in understanding some of the immunoregulatory mechanisms induced by combined therapy in MS.