ABSTRACT Chlamydia pecorum is an important intracellular bacterium that causes a range of diseases in animals, including a native Australian marsupial, the koala. In humans and animals, a gamma interferon (IFN-γ)-mediated immune response is important for the control of intracellular bacteria. The present study tested the hypotheses that C. pecorum can escape IFN-γ-mediated depletion of host cell tryptophan pools. In doing so, we demonstrated that, unlike Chlamydia trachomatis , C. pecorum is completely resistant to IFN-γ in human epithelial cells. While the growth of C. pecorum was inhibited in tryptophan-deficient medium, it could be restored by the addition of kynurenine, anthranilic acid, and indole, metabolites that could be exploited by the gene products of the C. pecorum tryptophan biosynthesis operon. We also found that expression of trp genes was detectable only when C. pecorum was grown in tryptophan-free medium, with gene repression occurring in response to the addition of kynurenine, anthranilic acid, and indole. When grown in bovine kidney epithelial cells, bovine IFN-γ also failed to restrict the growth of C. pecorum , while C. trachomatis was inhibited, suggesting that C. pecorum could use the same mechanisms to evade the immune response in vivo in its natural host. Highlighting the different mechanisms triggered by IFN-γ, however, both species failed to grow in murine McCoy cells treated with murine IFN-γ. This work confirms previous hypotheses about the potential survival of C. pecorum after IFN-γ-mediated host cell tryptophan depletion and raises questions about the immune pathways used by the natural hosts of C. pecorum to control the widespread pathogen.