The interaction between cytokines such as interleukin-12 ( IL-12 )and IL-18 plays an important role in malaria pathogenesis and outcome , modulating the immunoresponce in Plasmodium falciparum ( P. falciparum ) malaria. This work aimed at detecting the plasma levels of IL-12 and IL-18 in P. falciparum malaria patients and to correlate the production of these cytokines with the severity of the disease .this study was conducted on two groups : Group I , consisted of 80 patients with P. falciparum malaria infection they were classified into two groups according to disease severity , 30 patients with severe malaria and 50 patients with mild malaria .Group II,consisted of 30 healthy persons as a control group. The levels of IL-12 and IL-18 were higher (16.2±8.3 pg/ml and 2682.8 ± 332.0 pg/ml , respectively ) in patients with mild malaria than in patients with severe form of the disease (12.3±6.42 pg/ml and 1226± 267.2 pg/ml respectively ) A positive correlation was observed between IL-12 and IL-18.These findings suggest that the production of these cytokines may be coregulated and both have an immunoregulatory effect on the immune response to P. falciparum infection , so can be used as a reliable parameter to predict the progression of the disease and may be used as an immunotherapy against P.falciparum malaria infection , especially in the early phase of the disease. Further studies are needed to find out the relation between these cytokines and individual forms and complications of P. falciparum malaria infection .