Sex differences in the susceptibility of Balb-c mice to Mycobacterium intracellulare infection were studied. When mice were given M. intracellulare intravenously, macroscopic lesions were considerably more extensive in the lungs, liver, and kidneys of male mice than in female mice. A significantly more marked growth of organisms occurred in these visceral organs of the male mice during the course of infection for as long as 16 wk after the challenge. This difference can be partly explained by the finding that the antimicrobial activity of host peritoneal macrophages is more potent in the female mice.