1 The contribution of endogenous endothelins to nociceptive responses elicited by ovalbumin (OVA) in the hind-paw of mice sensitised to this antigen (50 mg OVA þ 5 mg Al(OH) 3 , s.c., 14 days beforehand) was investigated. 1 mg). Treatment with BQ-123 (3 nmol, i.pl.) reduced only the hyperalgesic effect of compound 48/80, whereas BQ-788 (3 nmol) was ineffective. 6 Thus, immune-mediated Type I hypersensitivity reactions elicit mast cell-and endothelindependent nociception in the mouse hind-paw, which are mediated locally by both ET A and ET B receptors. The nocifensive response to antigen is amenable to blockade by systemic treatment with dual ET A /ET B or selective ET A receptor antagonists, but is sharply potentiated by systemic selective ET B receptor antagonist treatment. The apparently distinct roles played by ET B receptors in this phenomenon at local and other sites remain to be characterised.