Sixty-one patients with falciparum malaria were studied prospectively to determine the plasma concentrations of the lysosomal proteinase, polymorphonuclear leucocyte elastase (PMN-elastase) and their relationship to disease severity. The patients were divided into 3 groups; severe (parasitaemia > 5%) or vital organ dysfunction (n = 23), moderate (parasitaemia 1%-5% without complications) (n = 15), and mild (parasitaemia < 1%) (n = 23). The mean plasma PMN-elastase level in 10 healthy Thai volunteers was 49.5 (SD = 21.6) ng/ml (range 33-65 ng/ml). Plasma PMN-elastase concentrations on admission were elevated (> 2 x SD above normal) in all patients with severe malaria and were above 100 ng/ml in 86.6% and 65% of the moderately severe and mild patients respectively. PMN-elastase levels during the first 3 hospital days were significantly higher in severe malaria compared with the other 2 groups (P = < 0.001-0.013). The levels decreased as the patients became afebrile and aparasitaemic. Admission plasma concentrations of PMN-elastase correlated directly with bilirubin (rs = 0.50, P < 0.001), serum glutamic oxalacetic transaminase (rs = 0.54, P0.001), parasite count (rs = 0.62, P < 0.001), blood urea nitrogen (rs = 0.54, P < 0.001) and inversely with antithrombin III activity (rs = 0.54, P < 0.001) and the platelet count (rs = 0.58, P < 0.001). Polymorphonuclear leucocyte activation may contribute to the pathogenesis of severe malaria.