Ebola viruses are filamentous, enveloped, nonsegmented RNA viruses. Although most Ebola viruses, notably Ebola-Zaire virus, are highly infectious for primates and can cause severe haemorrhagic diseases, Ebola-Reston virus does not cause serious disease in humans. Microarray technology was employed to compare cellular gene responses to Ebola-Zaire and Ebola-Reston virus infection of primary human monocytes, the early targets of Ebola-Zaire virus infection. We found that approximately 200 of 1,400 human genes on the array exhibited changes in expression in response to Ebola-Zaire virus infection after 24 hours. Most affected genes were upregulated in their level of expression, including cytokine and chemokine genes (IL-1, IL-1, IL-6, IL-8, IL-15, MIP-1, MIP-1 and TNF), genes involved in regulation of cell cycle or apoptosis and other genes involved in signal transduction. The gene expression profile from Ebola-Reston–infected monocytes was totally different from that observed with Ebola-Zaire virus. The results from northern-blot or ribonuclease protection assays confirmed the array data. The possible influence of differences in cellular gene expression observed between Ebola-Zaire and Ebola-Reston viruses on the ability of these viruses to cause diseases will be discussed.