Several viruses interfere with the host immune response by infecting dendritic cells and by altering their functional activity. Here, we report that exposure to Human herpesvirus 8 (HHV-8) of human dendritic cell (DC) monocyte precursors resulted in impaired immature DC (iDC) formation as indicated by a reduced CD1a expression. In accordance, the immunostimulatory ability of such iDC was significantly reduced, as indicated by mixed lymphocyte culture (MLR) assays. The immunostimulatory functions of DCs were similarly inhibited by the UV inactivated viral stocks, suggesting that the virus binding is sufficient to determine the observed effect. Furthermore, HHV8 mediated inhibition of the DC allostimulatory function was present in lipopolysaccharide (LPS) matured DCs. A strong reduction of the expression of the costimulatory molecule CD80 on the surface of the virus-exposed cells was observed as well. Impairment of dendritic cell development and function might represent an important strategy used by HHV-8 to escape from the host defense mechanisms.