A high level of resistance of oral infection with Echinococcus granulosus eggs was stimulated in lambs by two or more subcutaneous injections of oncospheres given 14 days apart. The degree of resistance was significantly higher than that resulting from a single injection. Resistance was apparently stimulated by the activated oncosphere or a stage of cyst development prior to 14 days of age. Studies on oncospheres cultured in vitro in sera collected from animals during immunization or after oral challenge showed that most cysts were killed before 7 days of culture had elapsed. This confirmed the observation that resistance was stimulated by an early stage of cyst development. The in vitro test also showed that two injections of oncospheres resulted in a marked increase in the lethal effects of serum. These lethal effects decreased with time, providing circumstantial evidence that the high degree of resistance stimulated by two or more injections may only be transient.