Dengue fever is clinically difficult to diagnose especially in the developing countries with no established diagnostic facility and could easily be mistaken for malaria, typhoid etc. This study was designed to determine the significance of these viruses in febrile illnesses. About 1948 serum samples from suspected cases of malaria and typhoid were collected from June 2001 to July 2002 in six ecological zones in Nigeria. 59 pools of Aedes Spp from Rain forest were tested by RT-PCR and for virus isolation. MAC-ELISA was used to test all the sera for IgM and IgG antibodies. All IgM positive sera were further analyzed by RT-PCR and Plaque reduction neutralization test (PRNT). Thirteen (0.67%) of the1948 sera were positive for DEN 1and 2 IgM from 4 zones. Mixed infections of DEN-2 and WN virus observed in two samples, eventually had neutralizing antibody for WNV. Overall, PRNT and ELISA results for DEN were in concordance. Dengue IgG antibodies in Sahel savanna (81.7%), Rain forest (69.0%), and Wooded savanna (69.0%) were significantly different from Grass (38.15%) and Sudan (32.6%) savanna. One IgM positive serum had detectable RNA to DEN. Fourteen of 59 pools of Aedes spp showed viral RNA to DEN 1-4. The prevalence of the antibodies to these viruses and the ages as well as the gender of the patients was not significantly different. Misdiagnosis of DEN infection for malaria/typhoid has been detected.[Journal of American Science 2009; 5 (5): 129-134].(ISSN: 1545-1003).