Functional IL4-590 C/T polymorphisms and the relative amounts of IL4 and IFN-gamma were investigated in relation to severity of malaria in 110 and 169 Thai patients with complicated and uncomplicated malaria, respectively. The plasma IL4 and IFN-gamma levels were determined by ELISA and the IL4-590 C/T polymorphisms were genotyped. The IFN-gamma levels were significantly elevated in patients with complicated malaria in the initial stage of the disease before treatment compared to the levels found with uncomplicated malaria (231pg/ml versus 150pg/ml, p=0.0029), while the IL4 levels were significantly elevated 7 days after treatment (167pg/ml versus 81pg/ml, p=0.0003). Our study did not reveal any association between the IL4-590 C/T transition and the severity of malaria. However, a significant difference in the IL4 to IFN-gamma ratio between patients with complicated and uncomplicated malaria was observed only in patients with IL4-590 T allele homozygosity (geometric mean: 0.321 versus 0.613, p=0.0087 for TT allele). A significant inverse correlation between IL4 to IFN-gamma ratio and peripheral parasitemia was observed only in complicated malaria patients carrying TT genotype (r=-0.283, p=0.046). These results suggest that the IL4-590 C/T polymorphism may play a role in the balance between IL4 and IFN-gamma, as well as in the control of parasitemia, which in turn may alter the severity of malaria.