Although interferon (IFN) beta is a widely used disease-modifying therapy in multiple sclerosis (MS), the mechanisms responsible for its effects are not fully understood. Some studies demonstrated that IFNbeta induces nerve growth factor (NGF) secretion by astrocytes and by brain endothelial cells. In this study, we determined the production of various neurotrophins (brain-derived neurotrophic factor, BDNF; NGF; glial cell line-derived neurotrophic factor; neurotrophin 3; neurotrophin 4) by peripheral blood mononuclear cells (PBMCs) in relapsing-remitting (RR) and secondary progressive (SP) MS patients during IFNbeta treatment. There were no main variations in neurotrophin production either among all MS patients globally considered or in the group of SPMS subjects. Instead, in the group of RRMS patients who did not present clinical exacerbation of disease up to the end of the study, we found a significant increase in BDNF production as from 6 months after starting therapy.