Tuberculosis pleurisy was induced by inoculation of virulent (H37Rv strain or Erdman strain) or attenuated (H37Ra strain) green-fluorescent protein-expressing Mycobacterium tuberculosis into guinea pigs that had or had not been vaccinated with Bacille-Calmette Guérin (BCG). Pleural fluid and cells were analyzed for phagosome-lysosome (P-L) fusion, on the basis of confocal microscopy, intracellular and extracellular bacterial survival, and production of cytokine mRNA. BCG vaccination increased fluid volume and cellular accumulation, significantly enhanced P-L fusion, and significantly decreased intracellular bacterial survival in pleural-effusion macrophages of the guinea pigs infected with the 2 virulent strains. Furthermore, significant increases in interferon-gamma, transforming growth factor-beta, tumor necrosis factor-alpha, and interleukin-12p40 cytokine mRNA were seen in the pleural cells of the BCG-vaccinated guinea pigs.