The aim of the current study was to determine the gene expression profiles of human macrophages exposed to infectious Ebola virions using DNA microarray technology (reviewed in [20, 21, 22, 23, 24] ) and therefore elucidate virus-host interactions. Here, we determine the initial responses of human macrophages to Ebola virion exposure. In a first set of experiments, DNA microarray analysis was performed to determine gene expression profiles of human macrophages 1 h and 6 h after in vitro exposure to Ebola virions in comparison to mock-exposed cells. In parallel, macrophages were treated with LPS to assess the responsiveness of the cells and to compare the response to different stimuli as genes responding to both virions and LPS might highlight possible response pathways. In a second set of experiments, we distinguished between responses induced by virion binding/entry and responses that require virus gene expression, cellular signals occurring after virion entry by exposing macrophages to Ebola VLPs. We found that Ebola virions exposure, as well as exposure to VLPs can trigger most of the detected changes after 1 h of exposure, and thus independent of virus replication.