This study describe the levels of plasma Chitotriosidase (CHIT) activity in 62 African children with severe and uncomplicated Plasmodium falciparum malaria with respect to 140 healthy African children. Medially all children with acute malaria showed plasma CHIT activity levels higher than healthy control subjects (140 nmol/mL/h, range 13-521, versus 72 nmol/mL/h, range 14-150, p<0.0001). Although the distribution curve of plasma CHIT activity showed a bimodal behavior, both children with severe malaria (n=22) and with uncomplicated ?malaria (n=40) showed elevated levels of plasma CHIT activity (median 138 nmol/mL/h, range 13-521 and median 151 nmol/mL/h, range 13-491, respectively). The difference between the two groups was not significant. On the contrary a significant correlation was found between plasma CHIT activity and serum ferritin only in children with uncomplicated malaria, but not in children with severe malaria. Since it is generally accepted that P. falciparum infection is mediated by the immune system, only a synchronic macrophage response guarantees the favourable outcome of this infection. We do not know how the expression of the CHIT gene is regulated, but the lack of correlation between plasma CHIT activity and serum ferritin in African children with severe P. falciparum malaria suggests in a failure of the synchronic macrophage response an important determinant of disease outcome.