The venom from sea nettle (Chrysaora quinquecirrha) (1-10 micrograms/ml) produced an irreversible contraction of the isolated rat aortic ring that was slow in onset, increased with time, and reached maximum in about 10-20 min. The contraction was not inhibited by pretreatment with phenoxybenzamine, atropine, indomethacin, tetrodotoxin, ouabain, low Na+ or Na+-free medium, however, it was markedly decreased by the Ca2+ channel blockers, nifedipine and verapamil. In Ca2+-free medium, no increase in tension was produced by the venom. It is concluded that sea nettle venom causes a contraction of the rat aortic ring by increasing Ca2+ influx through the voltage-dependent Ca2+ channels.