The cattle tick, Rhipicephalus microplus, is a monoxenous tick that co-evolved with indicine cattle on the Indian subcontinent. It causes massive damage to livestock worldwide. Cattle breeds present heritable, contrasting phenotypes of tick loads, taurine breeds carrying higher loads of the parasite than indicine breeds. Thus, a useful model is available to analyze mechanisms that determine outcomes of parasitism. We sought to gain insights on these mechanisms and used RnA sequencing and Multidimensional Protein Identification Technology (MudPIT) to generate a transcriptome from whole larvae and salivary glands from nymphs, males and females feeding on genetically susceptible and resistant bovine hosts and their corresponding proteomes. 931,698 reads were annotated into 11,676 coding sequences (CDS), which were manually curated into 116 different protein families. Male ticks presented the most diverse armamentarium of mediators of parasitism. In addition, levels of expression of many genes encoding mediators of parasitism were significantly associated with the level and stage of host immunity and/or were temporally restricted to developmental stages of the tick. These insights should assist in developing novel, sustainable technologies for tick control. Rhipicephalus microplus, the cattle tick, is distributed worldwide 1,2. Hematophagy and physical damage caused by the tick's bites during a blood meal, as well as transmission of pathogens, including Babesia ssp. and Anaplasma marginale cause huge economic losses globally 3,4. R. microplus is a monoxenous tick, consequently it spends its 3-week parasitic cycle on the same host, thus confronting all stages of its host's immune responses 5. Ticks use an array of molecules from their saliva to attach to their hosts and neutralize host inflammatory and immune responses and saliva also facilitates transmission of pathogens 6-8. The current methods for controlling these ectoparasites use acaricides, which pollute the environment, contaminate food products and are selecting acaricide-resistant ticks 3. Thus, development of new technologies for controlling R. microplus is urgent. To date, two commercial vaccines, GAVAC and TickGARD, have been marketed to control cattle tick infestations 9,10. Their design is based on the Bm86 antigen, a gut protease and a so-called "concealed" antigen 11,12 , i.e., an antigen to which hosts are not exposed to during natural infestations, as opposed to salivary antigens. While ticks feeding on cattle vaccinated with either of these vaccines do become damaged and present with