We compared the defense mechanisms directed against Wuchereria bancrofti by a filaria susceptible mosquito, Culex pipiens, and a refractory one, Aedes caspius. The reciprocal deleterious effects of both the mosquito host and its parasite are reported. Anatomical and histological examinations of mosquitoes revealed minor differences in the general structure of the foregut of either species. The cibarial pump of Ae. caspius, however, lacked a cibarial armature and damage inflicted to some of the microfilariae (mf) ingested by this mosquito was not mechanical. In contrast, the cibarial armature of Cx. pipiens consisted of 24 delicate teeth which did not seem to affect ingested mf. The peritrophic membrane (pm) did not constitute a significant barrier to mf migrating through the midgut wall of either mosquito. Indeed, mf forced their way out into the hemocoel, immediately after they have been ingested, and up to 60 min post-feeding, when the pm was still thin and soft. It hardened 16 h post-feeding. Traversing mf perforated the pm and displaced the basement membrane. Within the thorax of Cx. pipiens, the parasite completed its development synchronously. In contrast, mf ingested by Ae. caspius did not develop beyond the sausage stage, and many of these larvae were vacuolated. In both mosquitoes, parasitized thoracic muscle fibers were tunnelled and, only in Ae. caspius, their nuclei were pyknotic. No worm encapsulation or melanization was observed in either mosquito. It is concluded that defense lines to invading parasites in Cx. pipiens are insignificant, and that in Ae. caspius, the main barrier to parasite development resides within the thoracic muscles. In the absence of cellular evidence, it is suggested that such a barrier is physiological in nature.