SUMMARYIn vitro ccll-mediated immune responses lo rotavirus in humans were studied. Peripheral blood mononuclear cells (PBMC) of healthy adults proliferated in response to stimiihuion with the infectious and u.v.-inactivated Wa strain othuman rotavirus, showing a maximum response on day 7 of culture; however, cord blood lymphocytes failed to respond to rotavirus. A CTOSS-reactive proiiferative response of PBMC detected by stimulation with the NCDV strain of bovine rotavirus suggests the existence of epitopes common to both human and bovine rotaviruses. which are recognized by human T lymphocytes. The phenotype of the majority of activated lymphocytes was CD3 *4* 8 , indicating that the cells mainly activated were helper T cells. Culture supernatants of PBMC stimulated with rotavirus contained interleukin-2 (IL-2) and interferon-gamma (IFN-y). In addition, PBMC stimulated with rotavirus demonstrated significantly enhanced cytotoxic activity against natural killer (NK) sensitive K562 ceils as well as an NK-resistanl Epstein-Barr virusimmortalized lymphoblastoid cell line (LCL). Treatment of PBMC with anti-CDl6 or NKHIA monoclonal antibody, both of which react with most NK cells and lymphokine-activated killer cells and complement markedly reduced the cytotoxic activity against K562 and LCL. These results suggest that stimulation of human PBMC with rotavirus results in the prodtiction of tymphokines, such as IL-2 and IFN-y, by rotavirus-reactive helper T cells and that these lymphokines augment NK activity and generate other forms of non-specific eytotoxic human lymphocyte activity. These cellmediated immune responses observed in the present in vitro study might play an important role in protection and recovery from rotavirus infection.