Because nonhuman primates are much more closely related to humans than small animals typically used to study influenza, they have been used as models for human disease. In particular, rhesus macaques have been used to study pathogenesis and evaluate therapeutic and prophylactic strategies (see Baas et al., 2006 for review). In addition, the suitability of pigtailed macaques as models of influenza in the context of transcriptional studies has been evaluated (Baskin et al., 2004). A recent study examined the innate immune response in affected lung tissue with viral genetic material present (Baas et al., 2006). The authors used histopathological analysis of lung tissue, immunohistochemistry, viral and host gene expression by microarray analysis, proteomics, gene expression in circulating blood cells, and quantitative real-time RT-PCR to study individual animal responses until the end of the experiment. The infections were mild, without pneumonia or significant lung pathology. The investigators were able to demonstrate significant differences in gene expression within regions in influenza virus-induced lesions, based on the presence or absence of viral mRNA, and correlated them with transcriptional markers of early disease in peripheral white blood cells (Baas et al., 2006).