Abstract. The reemergence of malaria in the last decade in Madre de Dios, southern Peruvian Amazon basin, was accompanied by ecological, political, and socioeconomic changes related to the proliferation of illegal gold mining. We conducted a secondary analysis of passive malaria surveillance data reported by the health networks in Finally, health facilities located > 1 km from the Interoceanic Highway reported significantly more cases than health facilities within this distance (ratio = 16.20, 95% CI = 8.25, 31.80). Transmission of malaria in Madre de Dios is unstable, geographically heterogeneous, and strongly associated with illegal gold mining. These findings highlight the importance of spatially oriented interventions to control malaria in Madre de Dios, as well as the need for research on malaria transmission in illegal gold mining camps. BACKGROUND