The highly specific association between three-spined sticklebacks (Gasterosteus aculeatus) and the tapeworm Schistocephalus solidus is an excellent model system for studies on host parasite interaction. In order to investigate the putative immune manipulation by S. solidus we used infection success of the eye fluke Diplostomum pseudospathaceum as a proxy for immune competence of the host fish. We used F1 progeny of S. solidus from a Norwegian (highly virulent) and a German (low virulence) population and their respective lab bred sympatric stickleback hosts in a fully reciprocal cross infection experiment. Six different fish families were exposed to four different worm sibships or sham exposed as controls. The fish were coinfected with D. pseudospathaceum at five different time points (1, 3, 6, 9, 12 weeks post exposure to S. solidus). In each infection round, a pool of cercariae from several field-collected snail hosts were used to account for the strong effects of D. pseudospathaceum genotype specificities. Fish from every treatment group (i.e. fish family x S. solidus sibship combination) were individually exposed to 100 D. pseudospathaceum cercariae. The infection success of D. pseudospathaceum, i.e. the number of metacercariae in the sticklebacks’ eyes, was determined two days post exposure. We analyzed a total of 991 fish and found significant differences in their susceptibility to eye flukes between time points and between treatments within rounds, due to interaction effects of the origin of the tapeworm and the origin and sex of the fish. The main mechanisms of the infection phenotypes are now investigated by expression analysis of candidate genes of the innate and the adaptive immune system. Using this molecular approach, the underlying immune modulations of sympatric and allopatric host-parasite combinations can be studied in further detail.