Leishmaniasis in the Americas is transmitted by Lutzomyia spp., which have many animal reservoirs. Previous studies indicated potential changes in vectors of climate-related distribution, but impact outcomes need to be further studied. We report climatic and El Nino events during 1985-2002 that may have had an impact on leishmaniasis in 11 southern departments of Colombia: Amazonas, Caqueta, Cauca (Ca), Huila, Meta (Mt), Narino, Putumayo (Py), Tolima, Valle (Va), Vaupes (Vp), and Vichada. Climatic data were obtained by satellite and epidemiologic data were obtained from the Health Ministry. NOAA climatic classification and SOI/ONI indexes were used as indicators of global climate variability. Yearly variation comparisons and median trend deviations were made for disease incidence and climatic variability. During this period there was considerable climatic variability, with a strong El Nino for 6 years and a strong La Nina for 8. During this period, 19,212 cases of leishmaniasis were registered, for a mean of 4756.83 cases/year. Disease in the whole region increased (mean of 4.98%) during the El Nino years in comparison to the La Nina years, but there were differences between departments with increases during El Nino (Mt 6.95%, Vp 4.84%), but the rest showed an increase during La Nina (1.61%-64.41%). Differences were significant in Va (P = 0.0092), Py (P = 0.0001), Ca (P = 0.0313), and for the whole region (P = 0.0023), but not in the rest of the departments. The importance of climate change is shown by shifts in insect and animal distributions. These data reflect the importance of climate on transmission of leishmaniasis and open further investigations related to forecasting and monitoring systems, where understanding the relationship between zoonoses and climate variability could help to improve the management of these emerging and reemerging diseases.