The mechanisms behind the beneficial effects of interferon-beta1a (IFN-beta1a) and glatiramer acetate (GA) in the treatment of multiple sclerosis (MS) are still uncertain. Altered cytokine patterns have been suggested including inhibition of proinflammatory cytokines like interferon-gamma (IFN-gamma) and enhancement of anti-inflammatory cytokines such as interleukin-4 (IL-4). Twenty-nine patients with MS (10 untreated, nine treated with IFN-beta1a and 10 with GA) were investigated with elispot of peripheral blood mononuclear cells. Spontaneous and myelin induced (myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG)-14-39 and MOG 63-87) IFN-gamma, IL-4, IL-5 and IL-10 secretion was studied. We found a significant reduction of spontaneous IFN-gamma, IL-4 and IL-5, but no difference in IL-10 secreting cells in both groups of treated patients compared with the untreated patients. Myelin-specific responses showed a significant decrease of IFN-gamma and an increase of IL-5, but no change in IL-4 and IL-10 secreting cells in treated compared with untreated patients. Both treatment groups revealed similar cytokine secretion patterns except for a more pronounced decrease of both spontaneous and MOG 14-39 induced IL-4 secretion in the IFN-beta1a treated group. Thus, immunological effects of IFN-beta1a and GA were similar showing that disease promoting Th1 (IFN-gamma) cells were reduced while the potentially beneficial Th2 response (IL-4) was maintained.