We studied the interaction of RV with human peripheral blood mononuclear cells (PBMC) from adult volunteers. After exposure of PBMC to rhesus RV (RRV), T and B lymphocytes, NK cells, monocytes, and myeloid and plasmacytoid dendritic cells expressed RV non-structural proteins, at variable levels. Expression of these RV proteins was abolished if infection was done in the presence of anti-VP7 neutralizing antibodies or 10% autologous scrum. Supernatants of RRV exposed PBMC contained TNF-a, IL-6, IFN-a, IFN-y, IL-2 and IL-10. Plasmacytoid DC were found to be the main source of IFN-a production, and in their absence the production of IFN-y and the frequency of RV specific T cells that secrete IFN-y diminished. Finally, we could not detect RV-antigen associated with the PBMC or expression of RV non-structural proteins in PBMC of acutely RV-infected children. Thus, although PBMC are susceptible to the initial steps of RV infection, most PBMC of children with RV-gastrocntcritis arc not infected.