Antimicrobial activity in human monocytes infected with Mycobacterium tuberculosis has been difficult to demonstrate in vitro, and the molecular mechanisms allowing the bacteria to survive intracellularly are unknown. As a means to test the influence of bacterial products in the microbicidal activity of monocytes we have developed an infection model with Legionella pneumophila, which is killed by interferon gamma activated cells. We demonstrate that this model is useful because M. tuberculosis lysates inhibit one hundred fold the interferon gamma induced activity against L. pneumophila. Comparable degrees of inhibition are also detected when we use lysates from the less pathogenic Mycobacterium gordonae and the pathogenic Staphylococcus aureus, suggesting the participation of a common mechanism. This hypothesis is supported by the fact that the pattern of cytokine secretion is similar in all cases. A significant difference is, however, observed when we used lysates from the non-pathogenic Escherichia coli, which resulted in the recovery of low numbers of bacteria, probably because they induce the cell death of infected monocytes.