Most previous studies of Mediterranean spotted fever (MSF) have included cases that either were not laboratory-confirmed or were confirmed by the Weil-Felix test. The authors report the detailed clinical, laboratory and epidemiological features of 199 serologically-confirmed cases of MSF (by microimmunofluorescence). This work demonstrates that the disease is difficult to diagnose, especially at the beginning; that it can be fatal (2.5% of cases); and that a rapid and specific diagnosis is necessary to identify atypical cases. Epidemiological features such as season (summer essentially), presence of a dog, and travel in an endemic area (the Mediterranean Basin) are important in the diagnosis. In such cases fever associated with rash have to be considered and treated as MSF.