Common variable immunodeficiency (CVI) patients require regular intravenous immunoglobulin substitution therapy (IVGG). We studied eight patients; four of whom had adverse reactions to IVGG, and found that those coincided with elevated tumor necrosis factor-alpha (TNF-alpha) levels during infusion. Those reactions and TNF production were abolished by switching from one IVGG preparation to another in two patients. Reappearance of adverse reactions after switching preparation was preceded by a progressive rise in peak TNF levels in one patient.