Species interactions in its extreme form of reciprocal co-evolution of hosts and parasites generate and maintain biodiversity. We aimed at a better understanding of potentially different co-evolutionary trajectories of a vertebrate host, the three-spined stickleback Gasterosteus aculeatus, and its naturally infecting cestode Schistocephalus solidus on a large geographic scale. S. solidus highly specifically infects G. aculeatus as intermediate host and undergoes almost its complete somatic growth in the stickleback, sometimes even exceeding the fish’s weight. The parasite’s size serves as a proxy for virulence and the growth is assumed to be an adaptive trait. Using controlled experimental infections, we studied the infection phenotype of different sympatric and allopatric host-parasite combinations. Naïve lab-bred sticklebacks from a German and a Norwegian reference population were individually infected with single tapeworm larvae from ten different localities across the Northern Hemisphere. The infection success, the parasite’s size and fish condition and immunological parameters were determined to estimate virulence. We found clusters of worm populations with similar levels of virulence that correlate with geographic areas and with the parasite’s phylogeny. S. solidus strains grew generally larger in German fish, however, within each host population, we found similar clusters. These results emphasize that the parasite’s growth can better be linked to genetic clustering of S. solidus and ecological characteristics of each habitat than to latitude or geographical distance between the source populations. In order to learn more about the molecular mechanistic basis of this interplay, we are currently analyzing expression levels of stickleback immune genes in response to infection with the different parasite strains.