Cytomegalovirus (CMV) has been shown to exert suppressive effects on the immune response but also to have mitogenic properties. A bacterial product, protein A from Staphylococcus aureus (SpA) was chosen to study possible interactions in vitro between bacterial products and adherent cells incubated with infectious CMV and ultraviolet light (UV)-inactivated CMV. Small amounts of infectious CMV potentiated SpA-induced DNA synthesis and Ig secretion measured by induction of plaque-forming cells (PFC). The reason for this may be that CMV in small amounts may act in synergism with the non-specific mitogen SpA. UV-inactivated CMV did not influence these responses except for a markedly enhanced PFC induction with SpA in lymphocytes from seronegative individuals. This remarkable synergism with SpA was also seen in enriched B cells. No synergism was seen in lymphocytes from seropositive donors. Large amounts of infectious CMV markedly reduced SpA-induced immune responses. Preliminary data suggest that the immunosuppressive effects are mediated by an interleukin 1 inhibitory factor. CMV was not shown to be a polyclonal B-cell activator but may, possibly in small amounts, act as such together with bacterial products, which would explain certain autoimmune phenomena. To conclude, CMV could in interaction with a bacterial product generate both synergistic and suppressive effects on immune response.