The cane toad invasion in Australia provides a robust opportunity to clarify the infection process in co-evolved versus de novo host–parasite interactions. We investigated these infection dynamics through histological examination following experimental infections of metamorphs of native frogs (Cyclorana australis) and cane toads (Rhinella marina) with Rhabdias hylae (the lungworm found in native frogs) and Rhabdias pseudosphaerocephala (the lungworm found in cane toads). Cane toads reared under continuous exposure to infective larvae of the frog lungworm were examined after periods of 2, 6, 10 and 15 days. Additionally, both toads and frogs were exposed for 24 h to larvae of either the toad or the frog lungworm, and examined 2, 5, 10 and 20 days post-treatment. R. hylae (frog) lungworms entered cane toads and migrated through the body but were not found in the target tissue, the lungs. Larvae of both lungworm species induced inflammation in both types of hosts, although the immune response (relative numbers of different cell types) differed between hosts and between parasite species. Co-evolution has modified the immune response elicited by infection and (perhaps for that reason) has enhanced the parasite's ability to survive and to reach the host's lungs.