Schistosomiasis remains one of the most prevalent parasitic infections and has significant economic and public health losses in many developing countries. Understanding the host/parasite interactions is important, since questions arise concerning the susceptibility of snails to infection by respective trematodes and their specificity and suitability as hosts for continued parasite development. Thus the aim of this research is to extend our knowledge about the biological basis of the snail/parasite relationship with the hope of finding novel ways to disrupt the transmission of this disease. In the current research the compatibility/incompatibility of two types of snails,Biomphalaria alexandrina and Bulinus truncatus with their target and nontarget miracidia (Schistosoma mansoni and Schistosoma haematobium) was investigated histopathologically and also by identifying some host defense mechanisms against the invading parasite by biochemical analyses through the measurement of lipid peroxides, and the antioxidant enzymes glutathione reductase, superoxide dismutase and catalase in these snails. The results showed that the parasites invading the incompatible snail species were immediately recognized by the host hemocytes and encapsulated at an early stage of snail penetration , while those infecting the compatibile snails were well developed as mother sporocysts. The obtained data also demonstrated that lipid peroxides were increased in snails exposed to the noncompatible parasite while the antioxidant enzyme levels were elevated in snails exposed to the compatible parasite indicating the capability of the respective parasites to overcome the defense mechanisms generated by its host. The infection rate between each type of snail and its compatible parasite was higher than with the non-compatible parasite. Results of these experiments strongly support the hypothesis that endogenous expression and regulation of larval antioxidant enzymes serve a direct role in protection against external oxidative stress, including immune-mediated cytotoxic reactions. This may open new areas for investigating new immuno or chemotherapies or vaccines against the enzymes or products that the parasite releases or needs to survive within its host.