We have studied the susceptibility of beige (C57Bl/6/bgJ/bgJ) mice to a virulent strain of Mycobacterium avium complex (MAC) (101) by intravenous, intraperitoneal, intranasal, oral, and intrarectal routes. Consistent with our earlier findings, intravenous challenge resulted in high mortality and colony-forming unit (CFU) counts of recoverable organisms from spleens, lungs, livers, and lymph nodes, plus high levels of mortality. Intraperitoneal challenge resulted in high organ CFU counts but no mortality. Of relevance to the sexual practice of certain homosexual patients with AIDS is the intrarectal route of inoculation, which resulted in extensive involvement of the visceral organs with MAC disease. Multiple challenges by intravenous, oral, or rectal routes resulted in higher CFU counts than did single exposures.