The incidence of dengue fever (DF) is estimated to have increased 30-fold in the past 50 years. The incidence of dengue haemorrhagic fever (DHF), a life-threatening complication of DF, is also increasing. The need for better classification of the severity of dengue infections has been proposed in order to clarify different entities of dengue infections. We defined a class of patients with DF with bleeding tendency (DF w/B) to differentiate further the varying pathogenesis among DF, DF w/B and DHF. In a hospital-based study in Taiwan, we compared clinical features, biochemistry and immune mediators among patients with DHF, DF w/B and DF. Results showed that DF w/B patients, similar to DHF patients, had a higher rate of secondary dengue infection (P<0.001) as well as higher IL-10 (P=0.023) and lower IFNgamma (P=0.009) levels than DF patients. In contrast, DHF patients had significantly higher soluble vascular cell adhesion molecule 1 levels than DF w/B patients (P=0.038) and DF patients (P<0.001). This study provides new insight into the different immune mechanisms of DF, DF w/B and DHF. DF involves a Th1 reaction and DF w/B involves an altered Th2 reaction, whereas DHF involves an altered Th2 reaction and augmented vascular insult.