Intravenous immunoglobulins (IVIG) have been effective in reducing multiple sclerosis (MS) disease activity and improving disability scores. However, the mechanism by which this beneficial effect is achieved remains unclear. An effect of IVIG on pro- and anti-inflammatory cytokines which are thought to play a role in the disease process - has been postulated in a number of animal and ex vivo studies. Hence, we performed a study on 34 patients with secondary progressive (SP) MS being treated with monthly IVIG or placebo for two years according to the protocol of the ESIMS study. Clinical outcome measures and cytokine production (interferon gamma, tumour necrosis factor alpha, interleukin-4 and -10) were recorded in all patients and compared with respect to the treatment group. Against our expectations, IVIG did not reduce the relapse rate or the progression of disability or cytokine production. Our data argue against an enduring immunomodulating effect of IVIG, at least in SPMS.