OBJECTIVES: The aim of this study was to examine the mechanisms by which weather conditions, the incidence of Leptospira in reservoir populations, and various socio-ecological factors are driving the emergence of leptospirosis in Marseille, France. METHODS: Over the last 30 years our laboratory has surveyed all human cases of leptospirosis in Marseille using clinical, epidemiological, serological, and molecular tools. Data for the weather conditions in Marseille were collected from the official meteorological station, and garbage management strikes were monitored through the local press. Rats were trapped in alleys near to where the patients may have acquired leptospirosis. RESULTS: Three new cases of autochthonous leptospirosis are reported. The global tendency for rainfall showed a slight increase over the period under analysis. The index case of leptospirosis occurred after a heavy rainfall with flooding. Over the last 10 years Marseille has undergone 82 days of garbage management strikes. Leptospira DNA was detected in two of 11 rats. CONCLUSIONS: The emergence of leptospirosis has become a public health problem in Marseille, and is associated with a combination of heavy rainfall and garbage collection strikes in which garbage is left on the street and thereby contributes to the expansion of the rat population on the surface.