1. Studies have considered how intrinsic host and parasite properties determine parasite virulence, but have largely ignored the role of extrinsic ecological factors in its expression. 2. We studied how parasite genotype and host plant species interact to determine virulence of the protozoan parasite Ophryocystis elektroscirrha (McLaughlin & Myers 1970) in the monarch butterfly Danaus plexippus L. We infected monarch larvae with one of four parasite genotypes and reared them on two milkweed species that differed in their levels of cardenolides: toxic chemicals involved in predator defence. 3. Parasite infection, replication and virulence were affected strongly by host plant species. While uninfected monarchs lived equally long on both plant species, infected monarchs suffered a greater reduction in their life spans (55% vs. 30%) on the low-cardenolide vs. the high-cardenolide host plant. These life span differences resulted from different levels of parasite replication in monarchs reared on the two plant species. 4. The virulence rank order of parasite genotypes was unaffected by host plant species, suggesting that host plant species affected parasite genotypes similarly, rather than through complex plant species-parasite genotype interactions. 5. Our results demonstrate that host ecology importantly affects parasite virulence, with implications for host-parasite dynamics in natural populations.