In porcine (PCA) and bovine (BCA) coronary arterial strips, epidermal growth factor-urogastrone (EGF-URO) caused an endothelium-independent Ca-requiring contractile response that could not be attributed to the secondary release of agonists from neural elements. In these tissues, EGF-URO also potentiated the contractile actions of other agonists (prostaglandin F2 alpha, KCl or norepinephrine). Nonetheless, the responsiveness of the PCA and BCA preparations differed markedly in terms of 1) their sensitivity to indomethacin and dexamethasone (indomethacin and dexamethasone abrogated the PCA but not the BCA response), 2) their desensitization properties (the BCA rapidly desensitized, whereas the PCA did not) and 3) the order of potencies for EGF-URO and transforming growth factor-alpha (TGF-alpha) (in the PCA, EGF-URO was more potent than TGF-alpha, whereas in the BCA, the potency of TGF-alpha was greater than or equal to that of EGF-URO). Taken together our data document the presence of two distinct receptor signaling systems for EGF-URO in the PCA and BCA preparations, and our results support the hypothesis that distinct receptor subtypes for EGF-URO may be present in these two tissues.