Rocky Mountain spotted fever occurs during seasonal tick activity. A history of exposure to tick-containing habitats within the 3- to 12-day incubation period is a key epidemiological factor. The signs of fever, headache, myalgia, nausea, vomiting, and anorexia at onset of infection are difficult to distinguish from those of self-limited viral infections. Rash usually appears later and, if present, progresses through a sequence of stages and distribution that are never pathognomonic. The effects of disseminated Rickettsia rickettsii infection of endothelial cells include increased vascular permeability, edema, hypovolemia, hypotension, prerenal azotemia, and, in life-threatening cases, pulmonary edema, shock, acute tubular necrosis, and meningoencephalitis. In severe cases, fluid management is a challenge. The clinical diagnosis, which is difficult, is rarely assisted by laboratory findings because antibodies are usually detected only in convalescence, and immunohistologic methods for detection of rickettsiae are unavailable in most clinics. Doxycycline is the treatment of choice except for pregnant or allergic patients, who are treated with chloramphenicol.