Because intensity of infection was significantly increased in a substrain of Aedes aegypti selected for susceptibility to the filarial worm, Brugia malayi, experiments were designed to assess numbers of microfilariae (mf) ingested and midgut penetration by mf in this susceptible substrain as compared to a refractory substrain selected from the same parental stock. Refractory mosquitoes ingested significantly fewer mf than susceptible mosquitoes and significantly fewer numbers of mf penetrated through refractory midguts as compared to susceptible midguts. In 16.7% of the refractory midguts, no mf were able to penetrate the midgut and in three refractory mosquitoes over 250 mf were ingested, but no mf penetrated the midgut. These results indicate that permissiveness of the midgut for penetration by microfilariae can determine not only parasite intensity, but also prevalence of infection. The genetic basis for ingestion of mf and midgut penetration was assessed using restriction fragment length polymorphism markers and quantitative trait loci (QTL) mapping. This mapping identified a QTL on chromosome 2, idb[2,LF181] (idb, intensity determinant for Brugia), that seems to influence ingestion ability. This QTL is linked to a previously identified QTL for susceptibility to B. malayi, fsb[2,LF98], as well as to loci for susceptibility to the malaria parasite, Plasmodium gallinaceum, and yellow fever virus. These results suggest that this region of chromosome 2 contains one or more genes that influence susceptibility of A. aegypti to several mosquito-transmitted pathogens.