Rocky Mountain spotted fever (RMSF) is caused by the gram-negative bacterium Rickettsia rickettsii. It is the most severe rickettsial illness of humans; without treatment, the case fatality rate is 20%-30%.

The disease is transmitted most commonly via the tick bite of the Dermacentor (American dog and Rocky Mountain wood ticks), Rhipicephalus (brown dog tick), or Amblyomma (cayenne tick). Mucosal transmission can occur when contaminated by a crushed tick or by tick fecal matter. RMSF occurs over a wide distribution throughout the contiguous United States, but cases are most commonly reported from Arkansas, Missouri, North Carolina, Oklahoma, and Tennessee. RMSF can also be seen in northern Mexico and Central and South America. Over 90% of cases occur during April through September. The disease is more frequent in males and children.

The incidence of RMSF has been steadily increasing to an estimated 2000 cases per year, but the case fatality rates (at least in the United States) have been decreasing (attributed to enhanced recognition and early treatment).

Early clinical manifestations of RMSF include high fever, severe headache, myalgias, nausea, and vomiting. Later manifestations include rash, photophobia, confusion, ataxia, seizures, cough, dyspnea, arrhythmias, jaundice, and severe abdominal pain. Rash occurs more frequently in children and young adults than in older individuals. It is also seen earlier in the course of the disease than in older individuals. Thrombocytopenia and hyponatremia and acute respiratory distress syndrome with organ failure may also be seen. A serious complication of RMSF is rhabdomyolysis. Long-term sequelae include central nervous system deficits and amputations.