Experimental T‐cell‐mediated hepatitis induced by concanavalin A (Con A) involves the production of proinflammatory cytokines. Because interleukin (IL)‐10 is a potent anti‐inflammatory cytokine derived from macrophages and T cells and is produced within the liver, we investigated the role of IL‐10 in modulating the hepatotoxicity and the secretion of cytokines following in vivo injection of Con A. IL‐10 is produced early in the serum after Con A challenge. Neutralization of endogenous IL‐10 by monoclonal antibodies (mAbs) increases the secretion of tumor necrosis factor α (TNF‐α) (+111%), interferon gamma (IFN‐γ) (+92%), and IL‐12 (+730%) 8 hours after Con A injection, and increases the hepatotoxicity, assessed by serum alanine transaminase (ALT) (+174%) measurement and by histology, 24 hours after induction of hepatitis. Conversely, preadministration of recombinant IL‐10 reduces the production of these proinflammatory cytokines (‐47%, ‐80%, and ‐47% for TNF‐α, IL‐12, and IFN‐γ, respectively), and decreases neutrophil infiltration and ALT serum concentration (‐74%) 8 hours after Con A challenge. We conclude that IL‐10, either endogenously produced or exogenously added, has a hepatoprotective role in Con A‐induced hepatitis, through its suppressive property on proinflammatory cytokine production, and that it might be of therapeutic relevance in human liver diseases involving activated T cells.