The kinetics of gene expression and the cellular source of murine β-defensin–3 (mBD3) and murine β-defensin–4 (mBD4) were determined in mouse models of progressive pulmonary tuberculosis and latent infection induced by high or low infecting doses, respectively. During progressive disease, there was an initial rapid expression of both defensins by respiratory epithelial cells that correlated with temporary control of bacillary proliferation, but expression decreased during the later progressive phase of the disease. In latent infection, both defensins were expressed continuously, but they were suppressed after reactivation of the disease. Thus, mycobacterial infection induces the expression of mBD3 and mBD4, and both might participate in the control of mycobacterial growth