Thymopentin, a synthetic pentapeptide (Arg-Lys-Asp-Val-Tyr) corresponding to amino acids 32-36 of the thymic polypeptide thymopoietin, has been reported to block adrenocorticotrope responses to stress. The purpose of the present study was to explore potential antistress properties of a synthetic analogue of thymopentin, IRI-514 (Ac-Arg-Pro-Asp-Phe-NH2) using a behavioral response to a stressor. The behavioral response to social conflict stress (resident-intruder paradigm) was evaluated by the elevated plus-maze test of anxiety in adult Wistar rats. A single subcutaneous (SC) administration of IRI-514, 48 h before stress, dose-dependently reversed the anxiety-like behavior induced by the social stress. The effect of IRI-514 was present over an extended period (24-72 h) following SC administration and was maximally effective at a dose of 1 mg/kg. These results indicate that IRI-514 has a long-lasting modulatory effect on behavioral responses to a stressor, and suggest that thymopoietin-derived peptides may have a role in modulating both behavioral and neuroendocrine responses to stress.