IL‐12 and IL‐23, which share the IL‐12 p40 subunit, have been ascribed central roles in many autoimmune disorders. We describe here an anti‐IL‐12 (αIL‐12) auto‐vaccine that potentially blocks both factors in vivo. Immunization of mice with mouse IL‐12 coupled to OVA or Pan DR epitope (PADRE) peptide induced Ab directed against the IL‐12 p40 subunit, which prevented IFN‐γ production in response to IL‐12 administration in vivo. Experimental autoimmune encephalomyelitis, an IL‐23‐dependent disease model, induced in SJL mice with a proteolipid protein (PLP) peptide was almost undetectable after αIL‐12 vaccination. Myelin oligodendrocyte glycoprotein (MOG)‐induced disease in C57BL/6 mice was also significantly inhibited. This protection correlated with inhibited Th1 cytokine responses in vitro and with an increase in the IgG1/IgG2a anti‐PLP Ab balance. Detrimental consequences of αIL‐12 vaccination were evaluated in C57BL/6 mice infected with Leishmania major (L.m.). While delayed‐type hypersensitivity (DTH) suppression and immunoglobulin as well as interleukin production patterns reflected a major shift toward a Th2‐type response, L.m. growth was still significantly retarded as compared to that seen in susceptible BALB/c mice. However, vaccinated animals ultimately failed to control parasite expansion. These results suggest that some chronic autoimmune diseases may benefit from αIL‐12 vaccination at the expense of reduced, but not completely abrogated, cell‐mediated immunity.