Three new bufadienolide glycosides, orbicusides A-C, in addition to the known tyledoside C, have been identified as the toxic principles of Cotyledon orbiculata L. var. orbiculata. The structures (3), (5), and (6) for orbicusides A-C, respectively, with three ether bridges between the 4,6-dideoxyhexose moiety and the bufadienolide aglycone, were deduced from a detailed ¹H and ¹³C n.m.r. study.