High-dose intravenous immunoglobulin (IVIg) can increase blood viscosity in vitro and has been associated with cardiovascular or cerebrovascular thromboembolism. Because thromboembolic events were observed in two (3%) of 65 patients we treated with IVIg, we measured serum viscosity serially in 13 patients (five with amyotrophic lateral sclerosis [ALS], eight with IgM paraproteinemic polyneuropathy) before and immediately after each of three consecutive monthly infusions of IVIg. We correlated changes in viscosity with serial determinations of the total serum IgG, IgM, and IgA before and after each infusion. Serum viscosity increased after IVIg in all the patients by 0.1 to 1.0 centipoise (cp) (mean, 0.55 cp). In three ALS patients and in all the patients with paraproteinemic polyneuropathy, serum viscosity exceeded the upper limit of normal (normal, 1.5 to 1.9 cp) and increased as high as 2.6 cp. The increase in viscosity occurred immediately after completion of the infusion, declined over 1 month, and appeared to correlate best with the serum IgG level, which after the infusions was as high as 6,160 mg/dl (normal, 545 to 1,560 mg/dl). I conclude that IVIg increases serum viscosity and in many patients can cross the symptomatic threshold level. Because increased serum viscosity can impair blood flow and trigger a cardiovascular or cerebrovascular thromboembolic event, IVIg should be used judiciously and with concurrent monitoring of serum viscosity in elderly patients and patients with cryoglobulinemia, monoclonal gammopathies, high lipoproteins, or preexisting vascular disease.