Human B- and T-lymphocyte preparations were isolated by separating T lymphocytes that formed rosettes with sheep erythrocytes from unrosetted B lymphocytes. Pokeweed mitogen stimulates the proliferation of both B- and T-lymphocyte preparations. In contrast, phytohaemagglutinin stimulates little or no proliferation of purified B lymphocytes although it stimulates the proliferation of T lymphocytes. Lymphoid preparations containing both T and B lymphocytes are more responsive to both mitogens than are either T- or B-lymphocyte preparations. This observation suggested synergy between T and B lymphocytes in the response of unfractionated lymphocytes to mitogens. The basis for this synergy was shown to be the capacity of T lymphocytes to facilitate the proliferation of B lymphocytes cultured with pokeweed mitogen or phytohaemagglutinin. The activity of T lymphocytes is not dependent upon their proliferation or attributable to their release of mitogenic factors. With regard to the clinical evaluation of immune function, our results indicate that the proliferative response of human lymphocytes to phytohaemagglutinin or pokeweed mitogen cannot be directly related to the percentage of T lymphocytes in the lymphoid preparation.