Parasite modification of host behavior is a well established phenomenon; however, little is known about the modulatory mechanisms regulating such effects. This study examined the relationship between Eimeria vermiformis infection, nociceptive responses, and endogenous opioid peptide activity in male RML mice. Infected mice displayed increases in centrally mediated antinociceptive responses (i.e., analgesia, measured as the latency of a foot-lifting response to a 50 C surface) throughout the prepatent period. The level of analgesia declined following onset of patency on day 8 postinfection (PI). Opioids were implicated in the increased antinociceptive response of the infected mice as the response was blocked by administration of a prototypic opiate antagonist, naloxone (1.0 mg/kg), on day 7 PI when maximum levels of analgesia were noted. This indicates that the analgesia evident in the parasitized mice was associated with increased opioid activity. Analgesia is one of a variety of behaviors influenced by changes in opioid activity, thus these observations provide further support for the contention that other parasite-induced alterations in host behavior may, in part, be the result of alterations in the activity of opioid modulatory systems.