Prostaglandin F2 alpha (PGF2 alpha), at a concentration that did not induce vascular contraction (10(-9) and 10(-10) M), potentiated the dose-response curves to norepinephrine (NE) in rat mesenteric ring segments only when the endothelium was present. Moreover, PGF2 alpha, in both unrubbed mesenteric artery and mesenteric vascular bed, was able to increase the contraction to NE as well as the ratio of the amplitude of two NE-induced contractions under previously standardized conditions, in the absence of extracellular calcium. In addition, without extracellular Ca2+, PGF2 alpha increased in both tissues the refilling of Ca2+ induced by 80 mM KCl plus 1.5 mM Ca2+. The mechanism of this potentiation is unknown, but it may be related to cellular events including the intracellular Ca2+ mobilization. This study suggests that the endothelium plays a necessary role in PGF2 alpha potentiation of vasoconstrictor response, possibly through the release of an endothelial vasoconstrictor factor which probably increases the Ca2+ bioavailability for the contraction.