Technical Abstract: Arthropods transmit a variety of important infectious diseases of humans and animals. Importantly, replication and development of pathogen infectivity is tightly linked to vector feeding on the mammalian host; thus analysis of the transcriptomes of both vector and pathogen during feeding is fundamental in understanding transmission. Using Anaplasma marginale infection of Rhipicephalus microplus as the experimental model, we tested three linked hypotheses exploring the temporal and organ-specific nature of the tick midgut and salivary gland transcriptomes during feeding and in response to infection. Numerous R. microplus genes were regulated in response to feeding. Genes were differentially regulated between the midgut and salivary gland and there was a clear progression in regulated gene expression in the salivary gland over time. In contrast, relatively few tick genes were specifically regulated in response to A. marginale infection. The genes regulated in response to infection were predominantly annotated as hypothetical or were genes of unknown function. Notable among the genes with informative annotation was that several ribosomal proteins were down regulated, suggesting that there may be a corresponding decrease in translation. The hypotheses that R. microplus salivary gland and midgut genes are differentially regulated and that the salivary gland transcriptome is dynamic over time were accepted. This is consistent with and important for understanding the different roles of the two organs, the midgut serving as an initial site of uptake and replication while the salivary gland serves as the final site of replication and secretion. The minimal effect of A. marginale on the tick transcriptome in terms of the numbers of regulated genes and the fold of regulation supports the view that the vector-pathogen relationship is well-established with minimal deleterious effect on the tick. The small set of predominantly hypothetical genes regulated by infection suggests that A. marginale is affecting a novel set of tick genes and may provide new opportunities for blocking transmission from the tick.