Recent studies have demonstrated that different antigen-presenting cell (APC)–related factors in the microenvironment of a T cell may determine its profile and quantity of cytokine expression and production. We have therefore examined the effects of alveolar macrophages and peripheral blood monocytes on interleukin (IL)-5 production by peripheral blood CD4 + T cells from atopic people with asthma (AA), atopic people without asthma (AN), and nonatopic normal subjects (N). In response to allergen stimulation, IL-5 production was significantly enhanced by the addition of monocytes to CD4 + cell cultures in AA and AN patients (p < 0.05 and 0.01, respectively), but not in N subjects. In mitogen-stimulated CD4 + cell plus monocyte cocultures, there was a small increase in IL-5 production in all three groups (p < 0.05 for AN). In contrast, the addition of alveolar macrophages to parallel cultures significantly amplified IL-5 production only in AA patients (p < 0.05 or 0.01). Furthermore, IL-5 production by CD4 + cells in alveolar macrophage cocultures, stimulated by allergen or mitogen, was higher than that in monocyte cocultures in AA patients (p < 0.05). Conversely, in AN and N subjects, the IL-5 values for alveolar macrophage cocultures were lower than those for peripheral blood monocytes. In blocking studies, antibodies against IL-1 α, IL-1β, IL-6, or tumor necrosis factor-α differentially suppressed macrophage-enhanced IL-5 production (p < 0.05 for IL-1β and IL-6) and expression of the activation marker CD25 (p < 0.05 for IL-1 α and IL-6) by allergen-stimulated CD4 + cells in AA patients. These observations suggest that alveolar macrophages influence the quantity of IL-5 production by T cells in the airways and, as a consequence, the development of asthma in atopic individuals.