Serotonin (5HT) has been implicated in the pathogenesis of several arterial disorders. Experimental intrarenal infusion of 5HT has produced initial decreases, and later sustained increases in total renal blood flow in the dog, and flow limiting renal artery spasm in other species. We assessed renal angiographic responses to 5HT infused into one renal artery of nine dogs before and after treatment with indomethacin (I). On blinded assessment of arteriograms, 5HT-induced narrowing was detected (p less than 0.001), and the effect was accentuated by I (p less than 0.001). Ketanserin (K), a 5HT-2 receptor antagonist, reversed the arteriographic vasoconstrictor effect of 5HT in five I-treated dogs (p less than 0.05). Linear cortical defects and decreased contrast intensity were seen in the nephrogram phase during 5HT infusion after I. This appearance resembled the arteriographic findings in hemorrhagic shock, suggesting profound impairment of renal cortical perfusion. This study suggests that 5HT constricts visible renal arteries via interaction with the 5HT-2 receptor, and that this in vivo effect is modified by arterial synthesis of vasodilator prostaglandins in the anesthetized dog.