Mice were immunized against Salmonella typhimurium with graded doses of heat-killed (HK) and acetone-killed (AK) vaccines and then challenged by the oral or intraperitoneal routes with two doses of S. typhimurium. HK and AK vaccines gave good protection against an intraperitoneal challenge, but failed to protect against an oral challenge which is presumably the natural mode of infection. HK vaccine was as potent as AK vaccine in reducing the mortality rate among mice challenged by the intraperitoneal route but, unlike HK vaccine, AK vaccine was also able to reduce the infectivity rate. With a small intraperitoneal challenge dose it was observed that a gradual increase in vaccine dose is associated with a corresponding fall in mortality rate, but with a larger challenge dose an increase in vaccine dose was associated with a corresponding increase in mortality rates. It was concluded that the protective potency of this type of vaccine may partly depend upon the total amount of antigen in the animal, i.e. including both the vaccine and the challenge organisms, at a critical time after challenge.