We used human microarrays to examine gene expression in a rhesus monkey model of human Plasmodium vivax malaria (P. cynomolgi in Macaca mulatta). Whole-blood cells were collected for extraction of RNA before infection, during both the initial liver phase of infection and bloodstream infection, and during the course of 2 bloodstream relapses. Clustering analysis showed that similarities in gene expression were greater at similar stages of the protocol for the 2 different monkeys than for the same monkey at different stages of the protocol. Interestingly, a large number of genes involved in RNA processing showed distinct down-regulation during the initial liver phase of infection. When only up-regulated genes were examined, there was evidence of an increasing number of "defense response" genes as the infection evolved but not of "cytoskeleton" genes (P</=.001). These results demonstrate the value of microarrays for studying the response of the primate transcriptome to malaria infection; they suggest that the host response is modulated by groups of genes.