Leptin, a hormone synthesized mainly by adipocytes, can modulate the immune response and seems to be involved in the induction of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis (MS). However, the possible role of leptin in MS pathogenesis has not yet been elucidated. In this study we investigated the effect of leptin on cytokine production by peripheral blood mononuclear cells (PBMCs) of MS patients (either in the acute or in the stable phase of the disease) and healthy controls. We also analyzed leptin effects on cytokine production by monocytes in relapsing MS patients. Our data showed that leptin induced tumor necrosis factor-alpha, interleukin-6, and interleukin-10 production by PBMCs of patients in an acute phase of disease but not in patients in a stable phase or in healthy controls. Moreover, we found no effect of leptin in monocytes from relapsing MS patients. Therefore we conclude that leptin may modulate the MS inflammatory process during relapses.