Isolated rabbit ear arteries displayed rhythmic contractions when stimulated with alpha 1 agonist phenylephrine. These rhythmic responses were greatly attenuated by endothelium removal. However, contractions were sufficiently rhythmic in the arteries treated with NG-monomethyl-L-arginine, NG-nitro-L-arginine and indomethacin, synthetic inhibitors of endothelium-derived nitric oxide and prostanoids. Phenylephrine-induced rhythmic contractions were converted to tonic contractions by the blockade both of the voltage-dependent Ca2+ channel and the Ca(2+)-activated K+ channel by nifedipine and charybdotoxin, respectively. In contrast, glibenclamide, an ATP-sensitive K+ channel antagonist, did not alter the rhythmic contractions. These results suggest that endothelium may in part regulate the phenylephrine-induced rhythmic contractions in the rabbit ear artery, although endothelium-derived nitric oxide or prostanoids may not be involved in these responses. These endothelium-involved rhythmic responses may be attributed to the activation of the voltage-dependent Ca2+ channel and the Ca(2+)-activated K+ channel.