Cyclobuxine is a steroidal alkaloid which was extracted from Buxus microphylla var. koreana Nakai. Extracts of Buxus microphylla var. koreana Nakai have been used as folk remedies of several diseases, including malaria and venereal diseases. In the present study, the possible protective effects of cyclobuxine against 60 min ischemia and subsequent 30 min reperfusion in isolated rat hearts were investigated. Ischemia induced a marked decline in contractile force and a gradual rise in resting tension. Reperfusion of the heart for 30 min resulted in a poor recovery of contractile force. When the heart was perfused in the presence of cyclobuxine (100 and 1000 ng/ml), a significant suppression of mechanical failure was seen. Ischemia also induced an immediate release of ATP metabolites and a release of creatine phosphokinase during reperfusion. Cyclobuxine inhibited the release of ATP metabolites, and slightly prevented the release of creatine phosphokinase during reperfusion. The ultrastructural damages induced by ischemia and subsequent reperfusion were significantly suppressed by cyclobuxine.