Abstract. A quantitative genetic study of the ability of Aedes aegypti to propagate dengue-2 (DEN-2) virus in the midgut and in a disseminated infection in the head was conducted with a standard half-sib breeding design. Aedes aegypti aegypti and A. aegypti formosus differ markedly in oral susceptibility to DEN-2 virus. Mosquitoes were orally infected and, after an extrinsic incubation period of 14 days, virus titer (by tissue culture infectious dose, 50% endpoint) was determined in the midgut (MT) and head (HT). Body size as measured by wing length was not significantly different between infected and uninfected mosquitoes and was not correlated with MT or HT. The heritability for MT in both subspecies was 0.41 and was 0.39 for HT in A. aegypti formosus. In A. aegypti aegypti, HT appeared to be controlled by dominant alleles. The MT was not correlated with HT nor did MT determine whether virus disseminated out of the midgut. These results suggest that it is the barriers to infection and dissemination, independent of virus titer, that determine vector competence for DEN-2 virus.The four serotypes of dengue (DEN) virus are a major public health concern for many tropical regions, each year causing hundreds of thousands of cases of dengue fever and dengue hemorrhagic fever. 1,2 The primary vector of DEN viruses is the mosquito Aedes aegypti. Subspecies and strains of A. aegypti have been shown to vary phenotypically in their susceptibility to DEN viruses. 3 Aedes aegypti aegypti has a broad geographic distribution, and many studies have shown that it is a more competent vector of flaviviruses than A. aegypti formosus, which is distributed only in sylvan and rural areas of West Africa. 3,4 In a study of the vector competence of A. aegypti for yellow fever (YF) virus, patterns of susceptibility among different populations were correlated with genetic groupings identified by allozyme analysis, suggesting a genetic basis for this variation. 4 Similar phenotypic variation has been seen for DEN viruses in another important vector, A. albopictus. 5 When a mosquito takes a viremic blood meal, the virus encounters several barriers to infection. First, virus must establish an infection in the midgut by overcoming a midgut infection barrier (MIB). Following replication in midgut epithelium, virus must pass through a midgut escape barrier (MEB) and replicate in other tissues (disseminated infection). Finally, virus must infect the salivary glands and be shed in saliva to be transmitted to the next vertebrate host.The genetics of MIB, MEB, and disseminated infection in A. aegypti for DEN virus and other flaviviruses are not well understood. Genetic studies of vector competence to date have primarily used selection protocols to produce susceptible and resistant lines, followed by crossing these lines to analyze the phenotype in F 1 offspring and in some studies, monitoring of susceptibility in F 2 and backcross generations. Miller and Mitchell 6 selected lines of A. aegypti that were completely refractory or highly susceptible to...