Since the mature egg is the pathogenic unit in schistosomiasis, sterilizing agents. by inhibiting egg-laying, should be therapeutic. The effects on Schistosoma mansoni of sterilization by X-radiation were studied in vivo, in mice, and in vitro. After the hepatic shift of adult S. mansoni produced by potassium antimony tartrate (PAT), the livers of mice were irradiated with 1,500 r. The worm and egg burdens, the survival times of the mice, and the morphology of the recovered worms, indicated that X-radiation at this dose had no effect. Groups of adult worms were exposed to various doses of X-ray in vitro and subsequently maintained in a medium consisting of 90% Medium No. 199 and 10% calf serum. Death from irradiation began 2 weeks after exposure. The LD50 was 68,000 r for males, and 59,000 r for females. As compared with nonirradiated controls, the rate of oviposition was inhibited 50% by 14,400 r and 90% by 100,000 r. The dose used in vivo inhibited egg-laying in vitro by only 4%. Sterilization of adults was measured indirectly by comparing the number of fertilized eggs (those maturing to the miracidial stage) laid after different X-ray doses with those laid by nonirradiated worms. Adults were sterilized 50, 90, and 100%, by 350, 1,000, and 5,000 r, respectively. The dose used in vivo was 92.5% sterilizing in vitro. The dose of X-rays used in vivo could neither sterilize adults nor inhibit egg-laying. However, by inhibiting the maturation of eggs, it should have extended the lives of the treated animals. Lack of efficacy in vivo may have been due to administering X-radiation too late in the course of the disease.