Smallpox prophylaxis studies having shown that the classical Jennerian type of vaccination may in some instances prove inadequate to prevent the development of the disease or may be contra-indicated for certain persons, attempts were made to evolve a method which could supplement or replace such vaccination. Investigations reported in this paper have demonstrated that the administration of gamma-globulin obtained from the sera of various animals hyperimmunized with vaccinia virus gives highly effective results in the prevention of different forms of experimental vaccinial infection. Encouraging results were also obtained with this gamma-globulin given prophylactically to 13 persons who had been in close contact with smallpox patients during an outbreak of this disease in Moscow in 1960. The author suggests that hyperimmune antivaccinia gamma-globulin of animal origin may also prove effective in the treatment of postvaccinal complications.