To ultimately define the virulence factors of rickettsiae, an understanding of the biology of the organism is essential. Comprehension of the pathogen-human interaction is critical to the development of control measures; and, in the case of vector-borne diseases, the role of the vector in maintaining and transmitting pathogens to vertebrate hosts is crucial to ultimate control. Recent studies have identified tick molecules that are likely involved in the tick-rickettsiae interchange, including tick response to infection and possible molecules exploited by rickettsiae during transmission events. We have further characterized several tick-derived molecules, including a histamine release factor, serine proteases, and lysozymes.