Organisms of the Mycobacterium avium complex cause disseminated blood-borne infection in patients with AIDS, who acquire the infection mainly through the gastrointestinal tract. Prior to causing infection, M. avium must colonize and invade the intestinal mucosa. This study examined the ability of several serovars of the M. avium complex to bind to and invade the HT-29 intestinal mucosal cell line and the HEp-2 laryngeal cell line. Logarithmic-phase M. avium was more efficient in binding and invasion than organisms in the stationary phase of growth. Bacteria incubated at 37 and 40 degrees C adhered to and invaded HT-29 cells more efficiently than bacteria cultured at 30 degrees C. The ability of M. avium to invade HT-29 and HEp-2 cells was inhibited when the cells were incubated with cytochalasin B prior to exposure to the bacterium, suggesting active participation of the mammalian cell in the process of internalization. Two protein kinase inhibitors, staurosporine and H7, blocked invasion of M. avium, and a specific tyrosine protein kinase inhibitor, genistein, also blocked the internalization but not the binding of bacteria. The findings suggest that M. avium binds to a specific receptor(s) on the epithelial cells and uses the cytoskeleton of the mammalian cell to become internalized.