To assess the validity of clinical criteria, we investigated 2096 outpatients diagnosed as malaria cases by nurses at a rural health subcentre in a highly endemic area of Papua New Guinea. 73% of the children < 10 years old had a positive blood slide for any species of Plasmodium and 32% had > or = 10,000 P. falciparum parasites per microL. For adults the frequencies were 51% and 9%, respectively. Stepwise logistic regression identified spleen size, no cough, temperature, no chest indrawing, and normal stools as significant predictors for a positive blood slide in children; no cough and normal stools predicted a positive blood slide in adults. Fever, no cough, vomiting, and enlarged spleen were significant predictors for a P. falciparum parasitaemia > or = 10,000/microL in children; in adults the only predictor was vomiting. In children the association of no cough and enlarged spleen had the best predictive value for a positive blood slide, and a temperature > or = 38 degrees C had the best predictive value for a P. falciparum parasitaemia > or = 10,000 microL. In adults, no major symptom had a good predictive value for a positive blood slide but vomiting had the best predictive value for a P. falciparum parasitaemia > or = 10,000/microL. When microscopy is not available, these findings can help in areas of high endemicity to determine which patients with a history of fever are most likely to have malaria and, more importantly, for which patients another diagnosis should be strongly considered.