C57BL/6 mice produce antibodies to bovine insulin (Bins) but not porcine insulin (Pins). Although insulin-specific, CDST cells inhibit antibody responses to Pins, insulin-specific, CD4T cell clones can be isolated from C57BL/6 mice immunized with either Bins or Pins. Most Bins induced clones respond to Bins but not Pins and they produce primarily IL-4 and IL-10. By contrast, clones induced with Pins respond to both Bins and Pins. The latter clones produce IL-4, IFNy, IL-10 and IL-2 when stimulated with ConA or Bins. Pins induces fewer lymphokines that are produced at lower concentrations in ThO clones than does Bins. These results suggest that expression of lympnokine genes in ThO clones may be independently regulated. These results also raise the possibility that CDST cells might inhibit the helper activity of ThO but not TH2 T cells. Alternatively, CDST cells might prevent the development of porcine insulin-specific, CD4Th2 cells thereby decreasing the number of efficient helper T cells and antibody responses.