Opioid peptides affect different immune functions. We present evidence that these effects could be mediated by the modulation of T_H1/T_H2 cytokine production. BALB/cJ mice were immunized with 50 or 100 μg of the protein antigen keyhole-limpet hemocyanin (KLH), and treated acutely or chronically with the opioid antagonist naloxone. One and 2 weeks after immunization, the production of cytokines by splenocytes was evaluated by in vitro restimulation with KLH. The acute and chronic treatment with the opioid receptor antagonist naloxone decreased the production of interleukin (IL)–4 by splenocytes of BALB/cJ mice. In contrast, IL-2 and interferon-γ levels increased after naloxone treatment. Finally, the opioid antagonist diminished the serum immunoglobulin G anti–KLH antibody titers. These results suggest that naloxone increases T_H1 and decreases T_H2 cytokine production. The effect of naloxone could be ascribed to the removal of the regulatory effects exerted by endogenous opioid peptides, which could therefore activate T_H2 and suppress T_H1 cytokines.