22-Methylene-3β-hydroxy-5β,20(S)-card-14-enolide (11) and 22-methylene-3β-hydroxy-5β,20(fi)-card-14-enolide (12) were synthesized from digitoxin (1). Attempts to prepare the 14β-hydroxy-22-methylene analogues were unsuccessful. The 20(R) isomer (12) was found in Na+,K+-ATPase inhibition studies to be twice as active as 14-dehydrodigitoxigenin (17). The 20(S) isomer (11) was significantly less active than 17. The hydrolysis of steroid 3β-tert-butyldimethylsilyl ethers was also found to be much more difficult than with nonsteroids.