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Background: Allergic asthma is increasing in black South Africans, a cohort with inherently high basal IgE levels. Atopy has been linked to an excess of the T helper 2 cytokines IL-4 and IL-5 relative to the T helper 1 cytokine interferon-γ (IFN-γ); however, most studies have utilized T cell clones. Studies on peripheral blood mononuclear cells (PBMC) have shown decreased IFN-γ release in patients with atopic dermatitis. It is uncertain whether this finding extends to atopic asthma. Objectives: To characterize cytokine release by mitogen-activated PBMC from Xhosa children and to investigate whether reduced IFN-γ release is a feature of atopic asthma and whether there is a relationship between cytokine profiles and asthma severity. Methods: Cytokine release and proliferation of phytohemagglutinin-stimulated PBMC from 10 patients with severe asthma and 14 patients with moderate asthma (highly allergic to house dust mites) and 17 healthy controls was assessed. Total serum, allergen-specific, and Ascaris -specific IgE was measured. Results: Proliferation did not differ between the groups. The release of IFN-γ was progressively decreased (and the IL-4/IFN-γ ratio increased) in the groups with moderate or severe asthma. Tumor necrosis factor-α release was reduced, but IL-4, IL-5, and granulocyte-macrophage–colony stimulating factor release was unchanged. The presence of Ascaris -specific IgE did not influence the cytokine profiles. Conclusion: Our study extends the findings observed for other atopic disorders and suggests that defective IFN-γ release is a generalized feature of atopic diseases. This study—the first to investigate both severe and moderate asthma, with the groups having similar atopic profiles—indicates that the extent of the defect in IFN-γ release might be related to asthma severity. (J Allergy Clin Immunol 1997;100:662-8.)