Abstract. Genetic compatibility, nonspecific defenses, and environmental effects determine parasite resistance. Host mating system (selfing vs. outcrossing) should be important for parasite resistance because it determines the segregation of alleles at the resistance loci and because inbreeding depression may hamper immune defenses. Individuals of a mixed mating hermaphroditic freshwater snail, Lymnaea ovata, are commonly infected by a digenetic trematode parasite, Echinoparyphium recurvatum. We examined covariation between quantitative resistance to novel parasites and mating system by exposing snail families from four populations that differed by their inbreeding coefficients. We found that resistance was unrelated to inbreeding coefficient of the population, suggesting that the more inbred populations did not carry higher susceptibility load than the less inbred populations. Most of the variation in resistance was expressed among the families within the populations. In the population with the lowest inbreeding coefficient, resistance increased with outcrossing rate of the family, as predicted if selfing had led to inbreeding depression. In the other three populations with higher inbreeding coefficients, resistance was unrelated to outcrossing rate. The results suggest that in populations with higher inbreeding some of the genetic load has been purged, uncoupling the predicted relationship between outcrossing rate and resistance. Snail families also displayed crossing reaction norms for resistance when tested in two environments that presented low and high immune challenge, suggesting that genotype-by-environment interactions are important for parasite resistance. In many plant-pathogen systems, resistance is determined by a genotype-specific interaction between the plant and the pathogen genotypes (reviewed in Thompson 1994;Kover and Caicedo 2001). Recently, genotype-specific interactions have also been found between hosts and their parasites in several animal systems (Lively 1989;Ballabeni and Ward 1993;Ebert 1994;Henter 1995;Ebert et al. 1998;Webster and Woolhouse 1998;Little and Ebert 1999;Webster 2001). Specific interactions of few host and parasite genes are therefore likely to be important in determining which individuals will suffer infections and which will remain healthy.Resistance is also determined by defenses that are independent of the parasite genotype (nonspecific defenses; Frank 2000). These host traits are often quantitative traits governed by several genes (e.g., innate immune system) and evolve through selection on heritable additive genetic variance. Phenotypic value (i.e., effectiveness) of this type of general defense may vary due to both host genotype and environment. For instance, when defense traits are energetically costly, resistance may be related to available resources (e.g., Oppliger et al. 1998;Wiehn and Korpimäki 1998;Ilmonen et al. 2000;Moret and Schmid-Hempel 2000;Rigby and Jokela 2000).Independent of costs, inbreeding may increase susceptibility if inbreeding hampers integri...