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Background The two main puzzles of this study are the onset and then sudden stopping of severe epidemics in western Provence (a highly malaria-endemic region of Mediterranean France) without any deliberate counter-measures and in the absence of significant population flux. Methods Malaria epidemics during the period from 1745 to 1850 were analysed against temperature and rainfall records and several other potentially relevant factors. Results Statistical analyses indicated that relatively high temperatures in early spring and in September/October, rainfall during the previous winter (principally December) and even from November to September and epidemics during the previous year could have played a decisive role in the emergence of these epidemics. Moreover, the epidemics were most likely not driven by other parameters (e.g., social, cultural, agricultural and geographical). Until 1776, very severe malarial epidemics affected large areas, whereas after this date, they were rarer and generally milder for local people and were due to canal digging activities. In the latter period, decreased rainfall in December, and more extreme and variable temperatures were observed. It is known that rainfall anomalies and temperature fluctuations may be detrimental to vector and parasite development. Conclusion This study showed the particular characteristics of malaria in historical Provence. Contrary to the situation in most other Mediterranean areas, Plasmodium falciparum was most likely not involved (during the years with epidemics, the mean temperature during the months of July and August, among other factors, did not play a role) and the population had no protective mutation. The main parasite species was Plasmodium vivax, which was responsible for very severe diseases, but contrary to in northern Europe, it is likely that transmission occurred only during the period where outdoor sporogony was possible, and P. vivax sporogony was always feasible, even during colder summers. Possible key elements in the understanding of the course of malaria epidemics include changes in the virulence of P. vivax strains, the refractoriness of anophelines and/or the degree or efficiency of acquired immunity. This study could open new lines of investigation into the comprehension of the conditions of disappearance/emergence of severe malaria epidemics in highly endemic areas. [ABSTRACT FROM AUTHOR]