Treatment with Interferon (IFN)-beta has been proposed as a therapeutic approach in multiple sclerosis (MS) patients, mostly in view of its immunomodulating actions. At the same time, evidence has been provided that MS patients exhibit polymorphonuclear cell (PMN) deficits, which can explain the increased susceptibility to infections in these subjects. Here, in 28 patients with relapsing-remitting (RR) MS under treatment with recombinant (r)-IFN-beta PMN polarization and PMN and monocyte (MO) phagocytosis and killing, as well as T-cell mediated antibacterial activity, were evaluated before treatment and over a period of nine months of treatment. Our results point out an enhanced rate of polarization (both "spontaneous" or N-formyl-methionyl-leucyl-phenylalanine-induced) in MS patients. After r-IFN-beta1b treatment the polarization rate was further increased. On the contrary, PMN and MO phagocytosis and killing were depressed in comparison to controls and values were further reduced by r-IFN-beta1b treatment. In patients T-cell mediated antibacterial activity was decreased at T0 and dramatically dropped in the course of r-IFN-beta1b therapy.