We investigated the potential effect of agonists of opioid receptors in the experimental model of Heligmosomoides polygyrus primary infection. BALB/c mice infected with H. polygyrus were treated with naltrexone, a non-specific antagonist of all three types of opioid receptors (mu, delta, kappa) prior to and during infection. The blockade of opioid receptors affected the pattern and level of immune response induced by H. polygyrus in the histotropic phase of infection, which suggests that an opioid receptor-linked mechanism is involved in the immune response of mice during this phase of infection. Down-regulation of the inflammatory response against fourth-stage larvae appeared to be by endogenous opioids influenced cytokines and nitric oxide production by macrophages in the peritoneum and in the gut as well as migration of leukocytes towards the antigens. Down-regulation of these mechanisms by opioid receptor agonists in vivo might account for the decreased resistance to H. polygyrus infection.