The progression of HIV infection has been associated with an increase in the plasma levels of total IgE. The mechanisms responsible for the increased IgE have not been elucidated. The type-1 and type-2 cytokine imbalance associated with HIV infection has been proposed as a possible mechanism for elevated IgE. The current study was undertaken to investigate the relationship between total IgE, type-1 and type-2 cytokines from a large HIV+ patient population. HIV+ patients were found to have elevated total IgE that inversely correlated with numbers of CD4+ T-cells. HIV+ plasma was also found to have decreased IFN-gamma and IL-12p70 levels as well as increased IL-10 levels compared to HIV-negative individuals. HIV+ patients with more advanced disease, as defined by absolute CD4+ counts, demonstrated more marked differences. Furthermore, the relative ratios of IFN-gamma:IL-10 and IL-12:IL-10 were decreased in HIV+ patients compared to HIV-negative individuals. The alterations in the plasma cytokines suggest a switch from a predominance of type-1 cytokines to type-2 cytokines that may enhance IgE synthesis. These data suggest that measurement of plasma IgE and/or cytokines may have prognostic or therapeutic monitoring value in HIV+ patients.