Parasitic wasps and flies (parasitoids) exert high mortality on caterpillars, and previous studies have demonstrated that most primary and secondary defenses do not protect caterpillars against parasitoids. We investigated the efficacy of tertiary defenses (i.e., immune responses) against parasitoids. Using a bead injection technique to measure the immune response and a 15-year database to measure parasitism, we compared the immune response for 16 species of caterpillars in nine different families. We found that caterpillar species with a strong immune response had the lowest incidence of parasitism, and when statistically compared to other defensive traits, the immune response was the best predictor of parasitism. Parasitoids either avoid attacking caterpillar species with a capacity for high levels of melanization or are killed once they have parasitized. In either case, the immune response is clearly one of the most effective defenses that caterpillars have against parasitism, and elucidating consistent predictors of variation in encapsulation could improve understanding of parasitism patterns in time and space and could enhance biological control efforts.