BACKGROUND: Malaria was endemic in the Rhone-Alpes area of eastern France in the 19th century and life expectancy was particularly shortened in Alpine valleys. This study was designed to determine how the disease affected people in the area and to identify the factors influencing malaria transmission. METHODS: Demographic data of the 19th century were collected from death registers of eight villages of the flood-plain of the river Isere. Correlations were performed between these demographic data and reconstructed meteorological data. Archive documents from medical practitioners gave information on symptoms of ill people. Engineer reports provided information on the hydraulic project developments in the Isere valley. RESULTS: Description of fevers was highly suggestive of endemic malaria transmission in the parishes neighbouring the river Isere. The current status of anopheline mosquitoes in the area supports this hypothesis. Mean temperature and precipitation were poorly correlated with demographic data, whereas the chronology of hydrological events correlated with fluctuations in death rates in the parishes. CONCLUSION: Nowadays, most of the river development projects involve the creation of wet areas, enabling controlled flooding events. Flood-flow risk and the re-emergence of vector-borne diseases would probably be influenced by the climate change. The message is not to forget that human disturbance of any functioning hydrosystem has often been linked to malaria transmission in the past.