A histologic study was performed on the livers of wild-type (WT), severe combined immunodeficient (SCID), hydrocortisone acetate (HC)-treated WT, and HC-treated SCID mice infected intravenously with 10⁵ CFU of Mycobacterium bovis BCG. It was found that infection progressed faster in SCID mice than in WT mice and that HC treatment caused exacerbation of infection in both types of mice. In all cases infection in the liver was confined to granulomas that were populated predominantly by macrophages. Higher levels of infection in HC-treated SCID mice, but not HC-treated WT mice, were associated with extensive infection and destruction of parenchymal cells at the margins of granulomas. The results indicate that in the absence of T-cell-mediated immunity and of HC-sensitive T-cell-independent defense mechanisms, macrophages are incapable of restricting BCG growth and of confining infection to their cytoplasm. Consequently, BCG bacilli are released into the extracellular environment, where they are ingested by neighboring parenchymal cells.