The mechanism whereby zinc regulates the in vitro antibody synthesis of human peripheral blood mononuclear cells was investigated. In a serum-free culture, zinc inhibited the pokeweed mitogen (PWM)-induced generation of immunoglobulin secreting cells (ISC) through an apparent non-specific augmentation of T-cells, which included CD4 and CD8 cells, as well as both CD8-Leu8+ and CD8-Leu8- cells. It was noted that CD4 cells were more stimulated than CD8 cells, and that CD8-Leu8- cells were more stimulated than CD8 Leu8+ cells. CD8-Leu8- cells inhibited the development of ISC. These findings indicate that, although zinc stimulates all T-cells, the relative potency of zinc differs among T-cell subsets; helper inducer T-cells appear to be most strongly stimulated.