The most important human disease vectors in the U.S. are the hard (ixodid) ticks, blood-sucking parasites of mammals that transmit a variety of diseases through direct inoculation of the host bloodstream during feeding. Several different human diseases are vectored through three different species of ticks in the state of Indiana. Although the disease-causing pathogens harbored by ticks have been extensively studied, there is almost nothing known about the other microorganisms harbored within ticks, as many of these microbes cannot be cultivated in the laboratory. Using high throughput 16S tag pyrosequencing and other cultivation-independent molecular approaches we have begun characterizing the structure and composition of the tick-associated microbial communities, and have identified a number of novel microorganisms, some that are endosymbionts (harbored within the cells of the tick) and some that are free-living guest commensals within the tick. We hypothesized and have now documented that certain tick-associated microbes can influence the ability of other microbes to colonize ticks. Human pathogens are important, but lower abundance constituents of these tick-borne communities and an understanding of the internal microbial ecology of the tick will help understand the colonization, stability and subsequent transmission of these pathogens