Epstein-Barr virus (EBV) is the etiological agent for acute infectious mononucleosis (AIM). It is also associated with certain malignant disorders in individuals with immunodeficiencies such as B cell lymphoproliferative disorder (BLPD). Our previous study with BLPD patients had demonstrated significantly higher serum IL-4 and IgE levels and significantly decreased IFN-alpha levels. These observations were consistent with the model of regulation of B cell growth by T cell-derived cytokines, in which IL-4 promotes B cell growth and switch to IgE synthesis whereas IFN-alpha and IFN-gamma inhibit these IL-4 mediated effects. Since AIM is also EBV associated, this study was designed to examine IL-4, IFN-alpha, IFN-gamma, IgE, and soluble CD23 (sCD23) serum levels in AIM patients. In this study we report for the first time that in contrast to BLPD patients, AIM patients did not exhibit increased levels of IL-4 and IgE; however AIM patients to exhibit decreased IFN-alpha levels and, additionally, also exhibit significantly higher sCD23 levels. This could result in B cell activation and have implications for the survival of the virus in B cells.