To test the hypothesis that the magnitude of plasma triglyceride changes could be related to the severity of falciparum malaria, we performed a retrospective case-control study from January 1999 to December 2000 among hospitalized patients with fever who were returning to France from the tropics. Plasma triglycerides were measured in patients with severe falciparum malaria ( n=13), mild falciparum malaria ( n=169), non- falciparum malaria ( n=20) and controls ( n=55). Triglyceride level was significantly higher in the malaria group than in controls [mean values were 2.17+/-1.43 mmol/l versus 1.30+/-0.70 mmol/l, respectively ( P<0.0001)]. Triglyceride level was also significantly higher in severe than in mild malaria [4.78+/-1.93 mmol/l versus 1.94+/-1.11, respectively ( P<0.00001)]. Hypertriglyceridemia (>1.80 mmol/l) was noted in all the patients with severe malaria, compared to 37% of patients with mild disease ( P<0.001). Although further studies are needed, these results define the relevance of hypertriglyceridemia as an indicator of the severity of falciparum malaria.