Abstract The present study examined the analgesic effects of the serotonin 5-HT 3 receptor antagonists ICS-205-930, MDL-7222 and GR-38032F in mice using acute thermal, mechanical and chemical pain tests. Subcutaneous administration (1–10mg/kg) of these agents did not produce analgesia in either the thermal or mechanical pain tests. However, ICS-205-930, MDL-72222 and GR-38032F all produced dose-dependent analgesia in the chemical pain test, that was not altered by systemic naloxone administration (1mg/kg, s.c.). Intracerebroventrlcular administration of these drugs (0.1–10μg) was ineffective in producing analgesia in acute thermal, mechanical and chemical pain tests. These results suggest that peripheral 5-HT 3 receptors play a role in chemical, but not thermal or mechanical nociceptive mechanisms.