One of the most obvious problems one perceives when working with Mycobacterium avium isolates is the vast array of phenotypes expressed with regard to colonial morphotype, serovar and particularly virulence. Thus whenever experimental data derived from different MAC isolates is compared the variety of this group of mycobacteria must always be considered. Another issue of concern is the extrapolation of in vitro data to the in vivo disease. We have reported, in the past, that survival in murine macrophage culture does not always correlate with survival in vivo (23). It is plausible therefore, that the pathways outlined in section 5.2 and figure 3 play a crucial role in the initiation of the innate immune response in general and that there are components of this response which are not expressed by IFN-gamma activated macrophages but which are necessary for bacterial control. In conclusion, we suggest that the initial control of MAC infection requires a healthy lung (or gut) architecture and that control by unactivated macrophages includes respiratory burst activity and also the sequestration of free iron away from the mycobacterial phagosome. Acquired immunity is important in controlling bacteria which have overcome the innate response and this control is mediated by cytokine activation of infected macrophages. Finally, we have described an animal model of infection in which uncontrolled bacterial growth occurs and in which lesions similar to those seen in AIDS patients develop.