1 Endothelin-1 causes ET A receptor-mediated enhancement of capsaicin-induced nociception in mice. We have assessed if this hyperalgesic eect of endothelin-1 is also accompanied by other proin¯ammatory eects, namely nociception and oedema, and characterized the endothelin ET receptors involved. 2 Intraplantar (i.pl.) hind-paw injection of endothelin-1 (0.3 ± 30 pmol) induced graded nociceptive responses (accumulated licking time: vehicle, 20.5+3.3 s; endothelin-1 at 30 pmol, 78.1+9.8 s), largely con®ned to the ®rst 15 min. Endothelin-1 (1 ± 10 pmol) potentiated ipsilateral capsaicininduced (0.1 mg, i.pl.; at 30 min) nociception (vehicle, 40.2+2.6 s; endothelin-1 at 10 pmol, 98.4+5.8 s, but 30 pmol was inactive), and caused oedema (increase in paw weight 5 min after capsaicin: vehicle, 46.3+2.3 mg; endothelin-1 at 30 pmol, 100.3+6.1 mg). 3 Selective ET B receptor agonists sarafotoxin S6c (up to 30 pmol) and IRL 1620 (up to 100 pmol) were inactive, whereas endothelin-3 (up to 30 pmol) induced only modest oedema. 4 ET A receptor antagonists BQ-123 (1 nmol, i.pl.) or A-127722-5 (6 mmol kg 71 , i.v.) prevented all eects of endothelin-1 (10 pmol), but the ET B receptor antagonist BQ-788 (1 or 10 nmol, i.pl.) was ineective. 5 BQ-788 (10 nmol, i.pl.) unveiled hyperalgesic eects of 30 pmol endothelin-1 and endothelin-3. Sarafotoxin S6c (30 pmol, i.pl.) did not modify endothelin-1-induced (10 pmol) nociception or oedema, but abolished hyperalgesia. 6 Thus, endothelin-1 triggers ET A receptor-mediated nociception, hyperalgesia and oedema in the mouse hind-paw. Simultaneous activation of ET B receptors by endothelin-1 or selective agonists can limit the hyperalgesic, but not the nociceptive or oedematogenic, eects of the peptide.