Intravenous immunoglobulins (IVIg) have been used successfully as an immunomodulating treatment for patients with inflammatory diseases of the central nervous system (CNS) including multiple sclerosis (MS). It was shown previously that IVIg could modulate the functions of microglia, the main immune cell in the CNS. We have compared five commercially available IVIg preparations on their capacity to modulate tumor necrosis factor (TNF)-alpha secretion and nitric oxide production in cultured microglia. All preparations induced a dose-dependent stimulation of TNF-alpha secretion as measured by ELISA. There were some small differences between preparations consisting of IgG, while the preparation enriched for IgM and IgA induced a considerably higher TNF-alpha production at 1 mg/mL and 10 mg/mL. Similar results were seen for nitric oxide production as measured indirectly by the Griess reaction. These results indicate that IgM/IgA-enriched IVIg may be a more potent immunomodulator than pure IgG preparations on inflammatory reactions in the CNS.