Epidemiological, clinical, and histopathological evidence suggests that black people are more susceptible to tuberculosis than are white people. The cellular basis of this putative susceptibility was investigated in vitro by comparing responses of blood-derived macrophages from black and white donors to experimental infection with virulent tubercle bacilli. Phagocytes from pairs of black and white donors were infected. The uptake and replication of the tubercle bacilli in these cells were measured by microscopic counts and by CFU counts of bacilli at 0, 4, and 7 days. The effects of donor serum, of 1,25-(OH)2-vitamin D3, and gamma interferon on the infection also were studied. Black-donor phagocytes killed more bacilli during phagocytosis than white-donor phagocytes did. However, the bacilli grew consistently and significantly faster in successfully infected macrophages from black than from white donors, especially in the presence of black-donor serum. 1,25-(OH)2-vitamin D3 gave significantly less protection against tubercle bacilli to macrophages from black donors than to macrophages from white donors. The permissiveness of the macrophages from the two races was affected equally by gamma interferon. These results demonstrate some inherent and environmental liabilities in the monocytic phagocytes and serum of black people compared with white people, which may contribute to their greater susceptibility to tuberculosis.