The importance of neuronal uptake processes in rat arteries and veins was compared using nisoxetine and fluoxetine, selective inhibitors for neuronal uptake of norepinephrine and serotonin, respectively. Nisoxetine (10(-7) - 10(-5) M) increased the sensitivity to exogenous norepinephrine in the portal and mesenteric veins (10-fold) and in the mesenteric artery (2.5-fold). Responses to field stimulation were also increased afternisoxetine in all three vessels. After nisoxetine, aortic responses to norepinephrine were unaltered and in all tissues, serotonin-induced contractions were reduced. Fluoxetine did not potentiate responses to norepinephrine or to field stimulation except in the mesenteric vein where sensitivity to norepinephrine was increased and the relaxation rate after field stimulation was prolonged. Although serotonin has been detected in blood vessels, fluoxetine did not increase vascular responses to serotonin. These studies suggest that rat mesenteric veins have a highly sensitive neuronal uptake mechanism of norepinephrine. Furthermore, these data provide indirect evidence against a functionally important serotonergic uptake process in rat blood vessels and suggest that neuronal uptake of serotonin does not exert a major role in terminating the vascular action of this biogenic amine.