To examine the modulatory role of interleukin (IL)-7 on intracellular growth of Mycobacterium avium complex (MAC), human macrophages were treated either before or after MAC infection with different concentrations of IL-7. At 100 pg/mL, 1 ng/mL, and 10 ng/mL, treatment with IL-7 before infection stimulated secretion of tumor necrosis factor-alpha (TNF-alpha) from MAC-infected macrophages (increase up to 40%) and resulted in dose-dependent reduction in the number of intracellular bacteria. Pretreatment with IL-7 did not inhibit the secretion of transforming growth factor-beta1 (TGF-beta1). IL-7 added to the macrophage monolayer 4 h after infection resulted in both the secretion of TNF-alpha from MAC-infected macrophages (up to 90% increase, P < .05) and antimycobacterial activity (up to 50% reduction in bacteria, P <.05); however, TGF-beta1 production was not inhibited. IL-7-dependent anti-MAC activity of macrophages was inhibited by anti-human TNF-alpha antibody. These results suggest that IL-7 may contribute to the regulation of the immune response against MAC.