Monocytes from the peripheral blood of nonimmune human subjects transformed in cell culture into macrophages with increased phagocytic capacity for killed typhus rickettsiae. When such cells were exposed to living virulent Rickettsia mooseri (Wilmington strain) or R. prowazeki (Breinl strain), or to the attenuated E strain of R. prowazeki, in the presence of medium containing normal human serum, all three strains readily entered the macrophage, but the subsequent fate varied according to strain and its virulence. Thus, R. mooseri grew readily to attain very high intracellular populations which eventually destroyed the macrophage in 3 to 5 days and escaped to infect other cells. Virulent R. prowazeki also grew at about the same rate for the first 2 to 3 days but then often abruptly ceased to multiply. Circumstantial evidence suggests a toxic effect on host cells by smaller numbers of R. prowazeki organisms than with R. mooseri. The attenuated E strain of R. prowazeki failed to grow in most cells and eventually disappeared, but did grow to substantial numbers in the very rare cell in some cultures, suggesting the presence of a few cells which may not be typical macrophages. The growth of R. mooseri in the macrophage cytoplasm was inhibited by chloramphenicol in the culture medium. When the drug was removed after 3 days, growth began after a lag period and assumed a normal rate.