Perennial malaria is a major public health problem for most coastal, lowland and foothill populations in Irian Jaya (western New Guinea), the largest and easternmost province of Indonesia. Malaria at higher elevations above 1,500 m is considered intermittent and highly unstable, providing a constant threat of epidemics. Beginning in late August 1997, a significant increase of unexplained deaths was reported from the central highland district of Jayawijaya. The alarming number of fatalities rapidly escalated into September, dropping off precipitously by late October. More than 550 deaths due to "drought-related" disease had been officially reported from the district during this 10-week period. The outbreaks occurred in extremely remote areas of steep mountainous terrain inhabited by primitive shifting agriculturist populations. Microscopical evidence and site survey data implicated malaria as the principal cause of the excess morbidity and mortality at elevations between approximately 1,000 and 2,200 m. The dramatic increase in malaria and associated deaths was indirectly related to the prolonged and severe drought created by the prevailing 1997-98 El Niño Southern Oscillation (ENSO) affecting the Australasian region. Clinical cases of malaria were described as severe, due, in large part to the low level of naturally acquired immunity (NAI) in these highland populations and the predominance of Plasmodium falciparum infection. Disease may have been further exacerbated by the population's compromised nutritional status because of severe shortages of staple foods affected by the drought. Based on a retrospective investigation, an 'a posteriori' epidemiological explanation of the probable, interrelated causes of the epidemic is presented. Beginning in late July 1997, drought conditions resulted in numerous, transient pools of standing water along zones of steep gradient streams normally associated with fast-flowing water. This permitted sufficient and rapid increases in vector populations (Anopheles punctulatus complex) that either could sustain recently introduced or intensified local low-level malaria transmission. Moreover, water and food shortages contributed to increased demographic movement and exposure to high risk malaria endemic lowlands, thus increasing the prevalence of human infections and infectious reservoirs in those populations returning to the highlands. The eventual rapid drying and elimination of the vector larval habitats along stream beds, combined with mass antimalarial drug distribution are believed, in part, to be responsible for the rapid decline of severe malaria and related deaths. Area delimited and isolated focal outbreaks of malaria are recognized as occasional, periodic events in these highlands. This epidemic produced great concern because of the broad regionalized extent of the problem, the culmination of many independent outbreaks occurring during the same period that overwhelmed the local health care and control capabilities. We predict communicable disease outbreaks, including malaria, may likely increase in periodicity in the Irian Jaya highlands as socioeconomic development and population movements increase. This investigation further underscores the importance of malaria and its impact on presumed NAI deficient highland populations. Furthermore, the association of ENSO-related climatic anomalies and heightened infectious disease transmission is illustrative of how rapidly changing local weather events can dramatically alter disease patterns. These circumstantial findings, albeit important, point to the urgent need for more definitive understanding of highland malaria dynamics, the development of a sustainable longitudinal surveillance system, and appropriate outbreak response capabilities for the highlands of Irian Jaya.