Rocky Mountain spotted fever is a life-threatening, tick-borne disease caused by Rickettsia rickettsii. This disease is rarely reported in Arizona, and the principal vectors, Dermacentor species ticks, are uncommon in the state. From 2002 through 2004, a focus of Rocky Mountain spotted fever was investigated in rural eastern Arizona. We obtained blood and tissue specimens from patients with suspected Rocky Mountain spotted fever and ticks from patients' homesites. Serologic, molecular, immunohistochemical, and culture assays were performed to identify the causative agent. On the basis of specific laboratory criteria, patients were classified as having confirmed or probable Rocky Mountain spotted fever infection. A total of 16 patients with Rocky Mountain spotted fever infection (11 with confirmed and 5 with probable infection) were identified. Of these patients, 13 (81 percent) were children 12 years of age or younger, 15 (94 percent) were hospitalized, and 2 (12 percent) died. Dense populations of Rhipicephalus sanguineus ticks were found on dogs and in the yards of patients' homesites. All patients with confirmed Rocky Mountain spotted fever had contact with tick-infested dogs, and four had a reported history of tick bite preceding the illness. R. rickettsii DNA was detected in nonengorged R. sanguineus ticks collected at one home, and R. rickettsii isolates were cultured from these ticks. This investigation documents the presence of Rocky Mountain spotted fever in eastern Arizona, with common brown dog ticks (R. sanguineus) implicated as a vector of R. rickettsii. The broad distribution of this common tick raises concern about its potential to transmit R. rickettsii in other settings. Copyright 2005 Massachusetts Medical Society.