Objective: To evaluate the expression of cytokines in both CD4(+) and CD8(+) T cells derived from peripheral blood of untreated multiple sclerosis (MS) patients with either relapsing-remitting (RR), secondary progressive (SP) or primary progressive (PP) MS and healthy controls (HC). Background MS is on immune-mediated disease and cytokines have been hypothesized to contribute significantly to disease progression. Compared to the relapse-onset (RR, SP) form of the disease, PPMS patients have different clinical, immunological and pathological features. Surprisingly, the ability of their circulating T cells to Produce immunoregulatory cytokines has not been extensively studied so for. Methods: Seventy-two MS patients (24 RR, 26 SP, 22 PP) and 34 HC were studied. Stimulated peripheral blood derived CD4(+) and CD8(+) T cells were analyzed for IFN-gamma, IL-2, TNF-alpha IL-4, IL-10 and IL-13 production. Results: MS patients express significantly more CD4(+) and CD8(+) T cells producing IFN-gamma compared to HC. Compared to the other forms of the disease, PPMS patients display a significant decrease in CD4(+) T cells producing IL-2, IL-13 and TNF-alpha and a significant increase in CD8(+) T cells producing IL-4 and IL-10. Conclusions: The data presented here demonstrate that patients with PPMS express less pro- and more anti-inflammatory cytokine producing T cells compared to the relapse-onset form of the disease, confirming the view on PPMS as a distinct disease entity.