Human alloreactive helper T cell clones were isolated from a secondary mixed lymphocyte reaction by limiting dilution in the presence of irradiated stimulator cells and T cell growth factor (interleukin 2). When cultured with B cells and macrophages possessing the relevant alloantigens, the T cell clones proliferated and induced a strong B cell activation with production of high immunoglobulin levels. Limiting dilution of the B cells from the peripheral blood showed that about one in 5-10 can be activated to produce IgG, one in 10 IgM, one in 20-40 IgA and one in 2000-5000 IgE. Following stimulation by the relevant alloantigen, the clones were able to help also B cells that lacked the alloantigen, indicating that a direct T-B cell interaction is not required. This method is particularly interesting because it is suitable for the clonal analysis of a B cell subset that is triggered in the absence of antigen by an unrestricted T cell help.