A new class of antigen-specific killer cells that combines the features of antibody-mediated and cell-mediated immunity was designed. The principle and feasibility of this strategy are illustrated by creating an antigen-specific killer cell to produce and secrete targeted antibody-toxin molecules that recognize and kill human immunodeficiency virus (HIV)-1-infected cells. The transduced lymphocytes, which were able to produce and secrete the targeted toxin proteins, remained viable due to the lack of the target antigen on the cell surface. These transduced cells were found to have selective and potent cytotoxicity to the HIV-infected cells. This approach combines the specificity of antibodies, extreme potency of toxins, and effector-cell properties of T-cells to generate a new class of potent antigen-specific killer cells, which may have broad applications for the treatment of viral infection and other diseases. This study demonstrates the principle that mammalian cells can be genetically modified to produce targeted toxins, indicating that in vivo production of targeted toxins can be achieved to locally or systematically destroy targeted cells.