We used microarrays and real-time reverse transcription-PCR to analyze the global transcriptional response of Mycobacterium tuberculosis to low pH in vitro, which may mimic an environmental signal encountered by phagocytosed mycobacteria. Eighty-one genes were differentially expressed > 1.5-fold, including many involved in fatty acid metabolism. The most highly induced genes showed homology with nonribosomal peptide synthetases/polyketide synthases.