Toll-like receptors (TLRs) play important roles in the immune system and have been shown to cause expression of cytokines and induce inflammation. Several studies have demonstrated that Toll-like receptors contribute to chronic inflammation and autoimmunity. There is some indication that polymorphisms of Toll-like receptors 3 and 9 may contribute to multiple sclerosis (MS) pathogenesis although the exact role of the TLR remains unclear. This study was undertaken to detect functional differences in TLR signaling between normal controls and patients with MS. Specifically, the ability of cells from MS or normal donors to respond to TLR 1/2, 3, 7, 8, and 9 agonists was evaluated by examining interferon gamma production as well as TNF-alpha, IL-12 and INF-alpha transcription.