Intravenous immunoglobulin (IVIG) has several effects on the immune system that could have a beneficial influence on disease processes in multiple sclerosis (MS). Four double-blind trials in relapsing-remitting MS have demonstrated that IVIG may reduce the relapse rate, progression and the number of gadolinium-enhancing lesions. However, these trials were smaller than the pivotal trials of interferon-beta and glatiramer acetate, and therefore, we performed a meta-analysis of the four trials in order to provide an overall assessment of the benefits of IVIG in relapsing-remitting multiple sclerosis in comparison with other drugs currently available for treatment of disease activity in MS. The meta-analysis showed a significant beneficial effect on the annual relapse rate (effect size -0.5; P = 0.00003), on the proportion of relapse-free patients (0.29 difference; P = 2.1 x 10(-8)), change in Expanded Disability Status Scale (EDSS) score (effect size: 0.25; P = 0.04), and a trend towards a reduction in the proportion of patients who deteriorated (P = 0.03). Each single study in the meta-analysis had its weaknesses, but all studies were positive regarding their primary end-point, and the results yield concordant evidence for reduction of relapse rate and progression. The ideal dosage of IVIG for treating MS needs still to be determined. In conclusion, IVIG may be a valuable alternative for treatment of relapsing-remitting MS, but can presently not be considered as a first-line treatment. IVIG could be considered in patients who do not tolerate or are unwilling to take the approved injectable medications, but additional studies are needed to establish the role of IVIG in the management of multiple sclerosis.