The interannual variation in malaria cases in Colombia between 1960 and 1992 shows a close association with a periodic climatic phenomenon known as El Niño Southern Oscillation (ENSO). Compared with other years, malaria cases increased by 17.3% during a Niño year and by 35.1% in the post-Niño year. The annual total number of malaria cases is also strongly correlated (r = 0.62, P < 0.001) with sea surface temperature (SST) anomalies in the eastern equatorial Pacific, a principal parameter of ENSO. The strong relation between malaria and ENSO in Colombia can be used to predict high and low-risk years for malaria with sufficient time to mobilize resources to reduce the impact of epidemics. In view of the current El Niño conditions, we anticipate an increase in malaria cases in Colombia in 1998. Further studies to elucidate the mechanisms which underlie the association are required. As Colombia has a wide range of climatic conditions, regional studies relating climate and vector ecology to malaria incidence may further improve an ENSO-based early warning system. Predicting malaria risk associated with ENSO and related climate variables may also serve as a short-term analogue for predicting longer-term effects posed by global climate change.