Pairs of specific pathogen free dogs were immunized with two injections of heat inactivated canine distemper virus (CDV) or one injection of a live CDV or live measles virus (MV) vaccine. Three unimmunized dogs were used as controls. All 9 dogs were challenged with virulent CDV (Snyder Hill strain). The three unimmunized dogs developed severe signs of disease with a lethal infection in one. The two dogs immunized with live CDV vaccine developed a strong humoral as well as cellular immune response after immunization and were protected against virus replication. Animals immunized with either inactivated CDV or modified live MV failed to develop a measurable cellular immune response after immunization and had a comparatively weak humoral immune response to distemper antigens. They showed mild signs of infection after challenge and responded with strong anamnestic cellular and humoral immunity. The measles vaccine immunized dogs had a moderate serum titer of measles hemolysin-inhibiting antibodies which, after exposure to distemper virus, was boosted to high levels. It is proposed that this response plays a role in the mitigation of the virulent distemper infection in these animals.