The uptake mechanism for the spirochete Borrelia burgdorferi, the causative agent of Lyme disease, was investigated by electron microscopy for human and murine phagocytes. Spirochetes of both a low- and a high-passage strain were preferentially internalized by coiling rather than by conventional phagocytosis. The spirochetes engulfed by coiling phagocytosis were found to disintegrate in an organelle exclusion zone without evident participation of lysosomes. Preincubation of B. burgdorferi with monoclonal antibody to the spirochetal OspA enhanced phagocytosis in general but did not consistently influence the uptake mechanism. Quantitative and kinetic differences concerning the phagocytic rate and mechanism were evident between cells from different lineages, different human individuals, and mice and humans. In general, when few phagocytes participated in spirochete uptake, the active cells displayed a high ratio of coiling versus conventional phagocytosis. These results suggest that coiling phagocytosis of B. burgdorferi plays a critical role in the control of spirochetal infection. More detailed studies on the molecular basis of this phagocytic mechanism may lead to new insights into the pathogenesis of Lyme borreliosis, a disease which is frequently characterized by the host's inability to eliminate the pathogenic spirochete.