Target cells of dengue virus(DV), monocyte and cells in macrophage linage, are professional nitric oxide producer. Recent investigation bu our group has show that nitric oxide is strong inhibitor of DV replication due to its ability to block DV-RNA dependent RNA polymerase activity. To elaborate an invitro effect of nitric oxide into natural dengue virus infection, the relationship between plasma nitric oxide and viral load in DV-infected patients was investigated. Plasma was obtained from OF and DHF patients of both primary and secondary infection. Level of nitric oxide was determinde by Griess's reagen while viral load was investigared by Real Time RT-PCR. Result showed that plasma nitric oxide of secondary DHF patients was significantly suppresses while viral load of this group of patient was significantly higher than other studied groups. Since this phenomenon occurs only in secondary-DHF patients, we then hypothesized that enhancing antibody(ADE) may be the mediator that suppressed nitric oxide production in secondary DHF patients. Thus the impact of ADE on nitric oxide prodution was detected in DV-infected monocytic cells. The significant reduction of nitric oxide production was found, 4.43+-2.62 and 8.36+-2.83 uM/ml, in the presence and absence of antibody, respectively. In contrast, the level of viral synthesis was highere in the presence of ADE, 3.77+-1.81*10^5 versus 3.64+-2.56*10^4 copies/ml. This result implied that ADE downregulated nitric oxide production which in turn increased viral replication. To determine the mechanism of antiviral radical downregulation, the effect of ADE onnan activation of iNOS gene transcription factor, STAT-1, was determined. Lysates of infected cells were electrophoresed. An activated form of STAT-1 was detected using specific antibody. Result demonstrated that activation of STAT-1 was blocked in the present of enhancing antibody. The information obtained from this study demonstrated one of the virulent mechanisms exerted by enhancing antibody during DV infection