1. A study of the various aspects of passive tetanus immunization and combined active and passive immunization in different animal species has been undertaken.
2. The criteria on which conclusions have been based consisted of titration of antitoxin serum levels and mouse and guinea-pig protection tests using a challenge of 20 M.L.D. of tetanus toxin.
3. A study of the rate of elimination of heterologous tetanus antitoxin in normal and sensitized animals showed that the latter eliminated antitoxin more rapidly from circulation after subcutaneous injection but no difference could be detected following intravenous administration. More important is the profound loss of serum antitoxin in both animal groups from the seventh day onwards.
4. The rate of elimination in humans receiving 1500 units of horse antitoxin subcutaneously was approximately the same in normal subjects and those who had been previously exposed to horse serum.
5. The interference of an active primary immune response by the simultaneous injection of antitoxin in rabbits was consistently more marked with fluid toxoid than with adsorbed toxoid. Thus, combined active and passive immunization of persons who have never been actively immunized, is not recommended, especially with fluid toxoid.
6. Administration of adsorbed toxoid 7 days or more after passive immunization with heterologous antitoxin does not interfere with the primary immune response.
7. Comparison of the immunizing potency in rabbits of fluid and adsorbed toxoids showed that the latter was far superior.
8. Homologous antitoxin was demonstrated in man and animals to be immunologically superior to the heterologous type in every respect. It persisted unchanged in a therapeutically active concentration for at least 3 weeks in humans and its protective action in guinea-pigs was at least 100 times greater than heterologous antitoxin. Since homologous antitoxin can be used in low doses it will not interfere with the primary immune response in combined immunization.
9. A recommended prophylactic dose of homologous antitoxin for man would be 200–250 units.