The threat posed to human health by arthropod-borne bacteria is most vividly demonstrated by the devastating epidemics caused by the plague. The diversity of pathogenic bacteria spread by arthropods is probably underestimated. Recently recognized infectious diseases such as Lyme disease and ehrlichiosis are caused by bacteria transmitted by arthropods. Bacteria which alternate between arthropods and mammals have to survive and thrive in diverse niches. Because of the desire to prevent diseases caused by these organisms, more emphasis had been placed on understanding their life in the vertebrate rather than in the vector. However, understanding how these pathogens develop within their vectors may lead to novel control strategies. The most extensive studies on the development of pathogenic bacteria within arthropods have been done with the agent of plague, Yersinia pestis, and its flea vector. Recent studies with Borrelia burgdorferi, the Lyme disease spirochete, have also revealed insight into vector-borne transmission of bacteria. The work on B. burgdorferi is reviewed here, and when appropriate, contrasted with Y. pestis. In the northeastern United States, the Lyme disease spirochete is maintained in a natural cycle involving rodents andIx-odes scapularis ticks. Larval ticks acquire B. burgdorferi when they feed on infected mice, and the spirochetes survive through the molts and are present in all subsequent stages (nymphal and adult) of the vector. Mice acquire B. burgdorferi from infected nymphs. Studies have focused on events that take place when infected ticks transmit spirochetes to mice. Infected nymphs have several hundred B. burgdorferi present extracellularly in the lumen of the gut. When nymphs attach and engorge on mice, the spirochetes multiply to reach densities of 100,000 bacteria in each tick. The gut is the primary site of B. burgdorferi residence and growth. Approximately 48 h into the blood meal, a few bacteria cross the gut epithelium into the hemocoel, invade the salivary glands, and then infect the host (1). Thus, B. burgdorferi, which primarily resides in the tick gut, invades the salivary glands only for a brief period during transmission. Similarly, Y. pestis resides in the lumen of an arthropod’s gut. In the gut of the flea, the bacteria multiply and form a plug that occludes the foregut and prevents successful feeding by the vector. During repeated, futile attempts at feeding by occluded fleas, Y. pestis are regurgitated into the mammalian host. Thus, although both Y. pestis and B. burgdorferi inhabit the gut lumen of their respective vectors, the two organisms use different routes of transmission. Y. pestis alters the feeding habits of the vector to increase transmission and eventually kills the flea, while there is no evidence that B. burgdorferi alters the behavior or survival of ticks. How do arthropod-borne bacteria adjust to the different niches they occupy? Several groups have found evidence of B. burgdorferi proteins expressed only at certain stages of the life cycle. Outer surface proteins (Osps) 1 A and B are two antigens coded on a bicistronic operon and abundantly expressed on the surface of spirochetes within unfed (flat) ticks. When nymphs feed, the majority of B. burgdorferi clear OspA and OspB from their surface and instead express OspC, a protein which is not expressed on spirochetes before tick engorgement (2, 3). Spirochetes that enter the host appear to continue expressing OspC and not OspA or OspB, because mice infected by tick bite rarely develop antibodies to OspA or OspB, while they readily seroconvert to OspC. However, during persistent infection of humans, OspA and OspB must be expressed (at least to …