A large body of experience has been compiled in different countries, documenting the efficacy of adenocorticotropic hormone (ACTH) for infantile spasms. This is important, because it may serve as a key for understanding this disorder, as well as for designing better medicines. However, significant discrepancies exist among studies originating in different countries regarding the relative efficacy of small or large ACTH doses. These differences may be caused by a number of factors, including potential genetic or environmental-related differences in the biology of the disorder or associated genetic components that determine responsiveness to ACTH. In addition, striking differences in the preparations used around the world may be responsible. These include bio-availability and extent of blood brain barrier penetration, efficacy in activating the efficacy-mediating 'ACTH receptors', the presence in certain preparations of competing analogs, and others. These issues should not detract from the overall agreement that ACTH might be the most useful medication currently available to treat WS.