Dengue epidemic virulence is thought to be conferred by various factors, including the genotype of the virus involved. Increased or decreased epidemic virulence has been associated not only with the introduction of type-2 (DENV-2) strains into the South Pacific, the Caribbean and South America, but also with newly emergent DENV-3 genotypes in Sri Lanka, and the year-to-year variation in the DENV-4 strains circulating in Puerto Rico. These observations indicate that there are inherent differences among viral genotypes in their capacity to induce severe disease, that is, their virulence potential. The present study involved a comparison of the complete genome sequences of DENV-1 viruses that had been isolated from cases of dengue fever (DF) or dengue haemorrhagic fever (DHF) that occurred in French Polynesia or Hawaii in 2001, when a virulent DHF-associated dengue epidemic was occurring throughout the Pacific region. Previous studies have identified putative virulence-associated motifs and substitutions in the DENV-2 genome, and the main aim of the present study was to identify similar changes in DENV-1 that may be associated with viral virulence. As no virulence determinants were seen, however, in any gene or untranslated region, it appears that genotype is not the sole determinant of virulence in DENV-1. Further studies, to compare DF- and DHF-associated strains of DENV-1 isolated from epidemics of variable virulence, in the same eco-biological context, are needed.