IL‐12 has been shown to be involved in the pathogenesis of Th1‐mediated autoimmune diseases, but its role in antibody‐mediated autoimmune pathologies is still unclear. We investigated the effects of exogenous and endogenous IL‐12 in experimental autoimmune myasthenia gravis (EAMG). EAMG is an animal model for myasthenia gravis, a T cell‐dependent, autoantibody‐mediated disorder of neuromuscular transmission caused by antibodies to the muscle nicotinic acetylcholine receptor (AChR). Administration of IL‐12 with Torpedo AChR (ToAChR) to C57BL/6 (B6) mice resulted in increased ToAChR‐specific IFN‐γ production and increased anti‐ToAChR IgG2a serum antibodies compared with B6 mice primed with ToAChR alone. These changes were associated with earlier and greater neurophysiological evidence of EAMG in the IL‐12‐treated mice, and reduced numbers of AChR. By contrast, when IL‐12‐deficient mice were immunized with ToAChR, ToAChR‐specific Th1 cells and anti‐ToAChR IgG2a serum antibodies were reduced compared to ToAChR‐primed normal B6 mice, and the IL‐12‐deficient mice showed almost no neurophysiological evidence of EAMG and less reduction in AChR. These results indicate an important role of IL‐12 in the induction of an antibody‐mediated autoimmune disease, suggest that Th1‐dependent complement‐fixing IgG2a anti‐AChR antibodies are involved in the pathogenesis of EAMG, and help to account for the lack of correlation between anti‐AChR levels and clinical disease seen in many earlier studies.