Summary: Complexes of polyadenylic and polyuridylic acids (poly A:U) were used to enhance the in vitro immune response of murine spleen cells to sheep erythrocytes. The effects of this potent adjuvant on the in vitro primary immune response were found to be similar to its in vivo action. Addition of poly (A:U) to cell cultures enabled an immune response to an antigen dose which was 100‐fold lower than the minimum dose of antigen required to stimulate an immune response in the absence of polynucleotides. In addition, the time required to obtain peak numbers of anti‐sheep erythrocyte haemolytic plaque forming cells was shortened by 1–1·5 days in the presence of poly (A:U). Poly (A:U) enabled as few as 10,000 thymus cells to collaborate with spleen cells from congenitally athymic, nu/nu mice in the immune response to sheep erythrocytes. Pre‐incubation of thymus cells or nu/nu spleen cells with poly (A:U) before culture demonstrated that poly (A:U) stimulated thymus influenced antigen reactive cells (T‐cells) but had no direct effect on antibody‐forming precursor cells (B‐cells).