We report the results of a comparison of several epidemiologic and ecologic parameters affecting the incidence and seroprevalence of Mediterranean spotted fever (MSF) in northern, central, and southeastern Marseille, an area endemic for this disease. In northern Marseille, the incidence of hospitalized patients with MSF was 24.2/100,000 persons compared with 9.8/100,000 and 8.8/100,000 for the central and southeastern regions, respectively. The seroprevalence in sera from blood donors, determined by microimmunofluorescence and confirmed by Western blot assays, was higher in the northern region than in the other two areas (6.7% versus 3.6% and 2.4%, respectively). This higher prevalence of MSF in the northern part of the city may be related to a greater tick exposure due to a higher number of dogs (32.6/100 inhabitants versus 28.4/100 and 27.2/100 in the central and southeastern regions, respectively) and a higher rate of infection of dogs in the northern region (51.4% versus 43.5% and 39.9%, respectively). The ratio of spotted fever group rickettsia-infected ticks was similar in both the northern and southeastern areas (14.8% and 13.4% respectively), but lower in the central area of the city (8.9%), leading to a higher risk of having MSF after a tick bite in the northern and southeastern parts of Marseille.