Background: FcG Receptors II (FcGRII) mediate a variety of biological response, including Antibodies Dependent Enhancement (ADE). The ADE theory shows that the presence of circulating dengue-specific IgG antibodies can enhance the viral entry trough FcGR and constitutes the largest risk factor for the individuals to develop of Dengue Hemorrhagic Fiver (DHF). An Arginine (R) to Histidine (H) substitution at position 131 of the FcGRIIa gene change the IgG binding affinity of the receptor with reduced opsonization of IgG2 associated with the arginine variant. The exceptional epidemiological circumstances in Cuba allow us to maintain a homogeneous sample with a similar history of natural dengue virus infections. In this work we investigate whether homozygosity for the arginine variant might be associated with a reduced risk of DHF caused by ADE and the subclass of IgG in the acute serum samples from individuals who suffered secondary infection to dengue 2 virus in the epidemic of Santiago de Cuba in 1997 with different clinical pictures. Methods: The Subclass of IgG were detected using Dot Blot in the soluble fraction and the immunocomplex fraction of the dengue acute serum samples kinetically collected. The DNA samples were studied to determine the polymorphism associated to Fc gamma receptor IIa. The FcGRIIa genotypes (R/R131, H/H131 and R/H131) and allelic frequencies were compared. Results: IgG1 are the predominant IgG subclass during the dengue acute infection even as a part of the immunocomplex or free in the serum. On the other hand IgG3 levels, only detected in the immunocomplex fraction, were observed in DF cases. The distribution of FcGRIIa genotype frequencies in Santiago de Cuba population showed the predominant RH genotype and the homozygocity for arginine variant did not found any protective effect associate to dengue infection in our population. Conclusion: The IgG subclass involved in dengue infection are IgG1 and IgG3 and the ADE phenomenon probably take place by the FcGRIIIa and FcGRIIIb associate with these IgG.