A study has been made of parabiotic mice in seven different strain combinations, all of them characterized by a one-way antigenic stimulus (parental ± F1 or syngeneic male ± female) (± = parabiosis). Mortality from parabiosis intoxication, which regularly is inflicted on the antigenic partner first, the rate of cross-circulation, and the parabiosis time necessary for obtaining a prolonged survival of skin allografts all reflected the varying antigenic strength of the strain combinations. Although the antimetabolite Amethopterin favourably altered the course of a particularly strong parabiosis combination (increased cross-circulation and diminished intoxication) it produced no discernible effect on the fate of subsequently grafted allogeneic skin.