Increased Th2 cytokine production in asthma is widely accepted, but excess production by asthmatic human airway CD4(+) T cells has not been demonstrated, nor has a relationship with disease severity. The importance of airway CD8(+) T cell type 1 and type 2 cytokine production in asthma is unknown. We investigated frequencies of IFN-gamma, interleukin (IL)-4 and IL-5 producing CD4(+) and CD8(+) blood and sputum T cells from normal subjects and subjects with asthma and compared between cell subsets, subject groups, and body compartments with and without in vitro stimulation and investigated relationships between cytokine production and asthma severity. Production of IL-4, IL-5, and IFN-gamma by unstimulated sputum CD4(+) and CD8(+) T cells was increased in subjects with asthma and related to disease severity, more for CD8(+) than for CD4(+) T cells. Frequencies of sputum CD8(+) T cells producing type 1 and type 2 cytokines were similar to those of CD4(+) T cells. In vitro stimulation polarized peripheral blood cytokine production toward IFN-gamma production, significantly more in subjects with asthma than in normal subjects. These data demonstrate increased type 1 and 2 cytokine production in CD4(+) and CD8(+) T cells in sputum and relate production to disease severity. Findings in blood did not reflect those in airways.