The effects of sinomenine (Sin) on isoprenaline and hist ami no dose-response relationships and calcium-mediated positive chronotro-pic time-response relationship were studied in isolated guinea-pig ri^lil atritui. Sin shifted isoprenaline and histamine doseresponse cuives to the right non-parallely and depressed their maximum and produced a noncompetitive antagonism. The pD'2 values were 3.48+ 0.08 and 3.63+0.04, respectively. It was different from B-receptor blocker propranolol and H2-receptor blocker cimetidinc. Sin as well as verapamil antagonized the positive chronotropic response to CaCl2. These results suggested that the negative chrouotropic effects of Sin did not result from blocked |3-and H2-receptor, but probably from antagonizing Ca2+ channel.