The Lyme disease spirochete, Borrelia burgdorferi, causes a disseminated infection in vivo, implying resistance to clearance by phagocytic cells. Because B. burgdorferi loses its infectivity after in vitro cultivation, the relationships between serial passaging of the organism in vitro, its susceptibility to elimination by phagocytes, and its infectivity were examined. When three different high-passage strains were incubated for 4 h at 37 degrees C with peripheral blood mononuclear cells, macrophages, or polymorphonuclear neutrophils, 45%-67% of the organisms were eliminated. In contrast, two low-passage strains were resistant to elimination by phagocytes, and only 5%-6% of the organisms were removed after 4 h. All five strains equally stimulated the neutrophil oxidative burst, indicating that evasion of phagocytes was not a result of avoidance of recognition by these cells. The two low-passage strains were infective when injected into mice, whereas the three high-passage ones were not. These observations indicate that infectivity of the Lyme disease spirochete correlates with resistance to elimination by phagocytic cells.