Mycobacterium avium is a common pathogen in AIDS patients and, in a large percentage of those patients, M. avium infection appears to be acquired via the gastrointestinal tract. M. avium is able to bind to and enter human and murine intestinal epithelial cells in vitro and in vivo. The invasion by and intracellular fate of M. avium in the HT-29 intestinal epithelial cell line was examined in an ultrastructural study. Bacterial contact with polarised cells was observed 10-15 min after monolayer infection and in polarised monolayers this always occurred in areas lacking microvilli. Contact with HT-29 cells did not appear to take place in a preferential area on the bacterial cell. Following invasion, M. avium was encountered within vacuoles containing either single or multiple bacteria; the latter evolved to contain only an individual bacterium. Vacuoles containing more than one bacterium were seen early in the infection and eventually underwent segmentation, with each bacterium occupying a vacuole. No bacteria were observed outside vacuoles up to 5 days after infection.