Recently, the Austrian Immunoglobulin in Multiple Sclerosis (AIMS) study showed patients with relapsing-remitting multiple sclerosis to benefit from repeated administration of intravenous immunoglobulin (IVIg). To provide a more detailed understanding of IVIg's action we performed further analyses on the time course of treatment effects and in regard to the impact of clinical disability at study entry on patients' response to medication. The AIMS trial was a randomized, placebo-controlled, double blind, multicenter trial. It included 148 patients (IVIg: 75; placebo 73) who suffered from relapsing-remitting MS, were 15-65 years old and scored from 1-6 on the Expanded Disability Status Score (EDSS). IVIg was given over 2 years in a monthly dosage of 0.15-0.2 g/kg body weight Within the first 6 months of the trial clinical disability of IVIg treated patients improved significantly from a baseline EDSS of 3.33 +/- 1.38 to a score of 3.05 +/- 1.73 (P=0.002). This improvement was retained over the subsequent 18 months of the trial (final EDSS: 3.09 +/- 1.62). In contrast, placebo-treated patients showed a slight trend for deterioration over the study period (baseline EDSS: 3.37 +/- 1.67; final EDSS: 3.49 +/- 1.83). IVIg treatment was associated with a significant reduction of relapses throughout the study which was independent of the patients' disability at baseline. The observation of clinical improvement in the early phase of IVIg medication may suggest the activation of repair mechanisms such as the promotion of remyelination while immunoregulatory effects would be expected as the cause of fewer exacerbations throughout the AIMS study. These hypotheses need to be tested in future trials.