Receptors mediating endothelin-induced contraction of myometrium were investigated in the human uterus. Endothelin-1 and endothelin-3 (10 pM to 0.3 microM) caused concentration-dependent contraction of myometrial strips. Endothelin-1 was approximately ten times more potent than endothelin-3, with pD2 values of 8.24 and 7.20, respectively. By contrast, two endothelin ETB receptor selective agonist, BQ 3020 (N-acetyl-[Ala11,15]endothelin-1-(6-21) and sarafotoxin 6c (up to 0.3 microM), did not induce contraction of human myometrium. The endothelin ETA receptor selective antagonist, FR139317 (1-hexahydroazepino-CO-Leu-D-Trp(CH3)-D-(2-pyridyl)alanine) (0.1, 0.3 and 1 microM), competitively antagonized the endothelin-1-elicited contraction, with a pA2 value of 7.10, whereas another endothelin ETA receptor-selective blocking drug, BQ 123 [cyclo(-D-Trp-D-Asp-Pro-D-Val-Leu)], behaved as a non-competitive antagonist. Pretreatment of myometrial strips with an endothelin ETB receptor selective antagonist, IRL 1038 ([Cys11-Cys15]endothelin-1-(11-21)), had no effect on contractions induced by endothelin-1. All these data indicate that only endothelin ETA receptors mediate endothelin-1-induced contractions of human myometrium.