Interferon alpha (IFNα) produced primarily by plasmacytoid dendritic cells (pDC) is a potent component of the anti-viral innate immune response, and modulates adaptive immunity. Primary control of IFNα production occurs at a cellular level and is highly dependent upon regulatory factors and their products. Recent studies have identified up-regulation of IFNα production mediated by the adaptive immune response in the form of immune specific IgG. These studies establish a role for the external control of IFNα production. The current work demonstrates that the Fc portion of IgG is a potent inhibitor of IFNα produced by pDCs in response to HIV, HSV, and VSV. Fc down-regulation occurs after IFNα production can be detected by bioassay, and suggests the existence of late regulatory events in the control of IFNα production. Down-regulation of IFNα is not caused by Fc-induced necrosis, apoptosis or neutralization of IFNα activity. Demonstration of Fc-mediated down-regulation of IFNα provides additional evidence of the role of IgG in the regulation of IFNα production.