The effect of intravenous immunoglobulin (IVIG) on various laboratory values was measured immediately before and after completion of serial monthly infusions of IVIG (2 g/kg) or an equal volume of placebo over 3-12 months, in 46 patients with neuromuscular diseases participating in controlled trials. Hematological, lymphocyte subpopulation, and chemistry values were analyzed and compared. After IVIG, but not placebo, a 34% reduction in lymphocytes was noted in 44/46 patients with a selective reduction of the T cells, but not the B or IL2R-positive cells. Counts returned to baseline within 30 days. Creatine kinase levels decreased by 23% and sedimentation rate increased by 275% after IVIG infusion. A nondilutional, artifactual, hyponatremia and hypomagnesemia was noted with IVIG but not placebo. We conclude that IVIG affects a variety of serum chemistry and hematological values either directly or artifactually by interfering with the laboratory method used for the assays. Transient lymphopenia is consistently seen, and may play a role in the immunomodulating effect of IVIG.