The influence of previous BCG vaccination on the bactericidal activity of isoniazid and rifampicin has been studied using serial counts of viable tubercle bacilli in the spleens and lungs of mice and guinea-pigs infected intravenously with M. tuberculosis, strain H37Rv. In mice, BCG vaccination decreased the bactericidal activity of isoniazid in the spleen, but did not affect its activity in the lungs, where immunity is less strongly expressed. BCG did not influence the bactericidal activity of rifampicin in either organ. In contrast, previous BCG vaccination in the guinea-pig increased the bactericidal activity of isoniazid and rifampicin in the spleen and lungs. The differences between the animal species might result from the immune response being mainly bacteriostatic in the mouse but bactericidal in the guinea-pig.