Dogs inoculated with Rickettsia rickettsii developed a clinical syndrome ranging in severity from a mild febrile exanthema to death within six days after inoculation. The severity of the disease appeared to be dose-related, and the signs were comparable to R. rickettsii infection in humans on a clinical and hematological basis. Dogs were rickettsemic for 10 to 14 days after infection. In most animals the level of rickettsemia was greater than or equal to 10(2.5) guinea pig intraperitoneal 50% infectious doses (GPID50). Infected dogs responded serologically as determined by indirect fluorescent antibody methods and were protected when challenged six to 12 months later with 10(7.0) GPID50 of the homologous strain of R. rickettsii. The monocyte culture technique was successfully used for the detection of rickettsemia, and the results compared favorably with those obtained by the guinea pig inoculation method of isolation.