Vascular responses to acetylcholine (ACh) and calcium ionophore A23187 were studied in the rings of the canine uterine arteries. Using uterine arteries of mature female mongrel dogs, ring-form specimens were prepared under a microscope. According to the Magnus' method the specimen was vertically fixed in Krebs-Henseleit solution and with a force-displacement transducer the isometric tension was determined. ACh and A23187 caused dose-dependent relaxation in the control, but it did not cause a response in endothelium-denuded preparations during contractions evoked by 3 X 10(-7)M norepinephrine. When pretreated with indomethacin (3 X 10(-6)M), a cyclooxygenase inhibitor, the maximal relaxation response induced by ACh was 73.35 +/- 14.53%, and pD2 values of 7.09 +/- 0.54, showing no difference from the untreated ones. On the other hand, preincubation with lipoxygenase inhibitors, nordihydroguaiaretic acid (NDGA) (3 X 10(-5)M) and AA861 (2 X 10(-5)M), prevented ACh-induced relaxation. The same trend was noted with the relaxation response induced by A23187. These results suggest that endothelium-derived relaxation of the canine uterine artery by ACh and A23187 may be mediated by a noncyclooxygenase metabolite(s). It was speculated that such inhibition of releasing EDRF has certain effects on the pathogenesis of toxemia and IUGR.