BACKGROUND: Zoonotic cutaneous leishmaniasis (ZCL) is endemic in many rural areas of the Southern and Eastern Mediterranean region where different transmission patterns of the disease have been described. This study was carried out in a region located in Central Tunisia and aimed to investigate the spatio-temporal dynamics of the disease from 1999 to 2004. METHODS: Incident ZCL cases were defined by clinical diagnosis, confirmed by a positive skin test and/or parasitological examination. Annual ZCL rates were calculated for 94 regional sectors that comprise the study region of Sidi-Bouzid. Spatial and temporal homogeneity were initially investigated by chi-squared tests. Next, spatial scan statistics were used to identify spatial, temporal and spatio-temporal clusters that display abnormally high incidence rates. A hierarchical Bayesian Poisson regression model with spatial effects was fitted to signify explanatory socio-geographic factors related to spatial rate variability. Temporal ZCL dynamics for the 94 sectors were described via a linear mixed model. RESULTS: A total of 15 897 ZCL cases were reported in the 6-year study period, with an annual incidence rate of 669.7/100 000. An outbreak of the disease was detected in 2004 (1114/100 000). Spatial clustering is evident for the whole time period. The most likely cluster according to the spatial scan statistic, contains seven sectors with abnormally high incidence rates and approximately 5% of the total population. ZCL rates per sector are mostly related to the urban/rural index; sectoral population density and the number of inhabitants per household do not appear to contribute much to the explanation of rate variability. The dynamics of the disease within the study period are satisfactorily described by quadratic curves that differ for urban and rural areas. CONCLUSIONS: ZCL rates vary across space and time; rural/urban areas and environmental factors may explain part of this variation. In the study region, the Sidi Saâd dam-constructed in the early eighties and identified by previous studies as a major reason for the first outbreak of the disease-seems to be still related to increased ZCL rates. The most likely spatial cluster of high incidence rates contains regions located close to the dam. Our findings of increased incidences in urban areas support the hypothesis of increased incidences in peri-urban environments due to changes in sandfly/rodent living habits over recent years.