Intravenous immunoglobulin (IVIg), a purified immunoglobulin fraction manufactured from the blood of healthy humans, is an FDA-approved treatment for many immune and inflammatory diseases. Recent studies have demonstrated that IVIg therapy has several positive effects on patients with Alzheimer's disease (AD). These include improving cognitive functions and lowering the level of soluble amyloid-β peptide (AβP) in the brain. Nonetheless, the mechanism by which IVIg mediates the clearance of AβP from the AD brain currently remains unknown. In this study we investigated the molecular basis for the direct and indirect effects of IVIg on AβP clearance using the BV-2 cellular microglia line. Specifically, we show that IVIg dissolves preformed AβP fibrils in vitro. Moreover, IVIg increases cellular tolerance to AβP, enhances microglial migration toward AβP deposits, and mediates phagocytosis of AβP. Thus, several mechanisms can be considered when examining the effects of IVIg. Our work supports the hypothesis that IVIg interferes by more than one mechanism in clearing AβP from the brains of Alzheimer's patients.