Interactions in size-structured populations are characterized by a mixture of predatory and competitive interactions dependent on the size of the individual organism. We analyzed this mixture of size-structured interactions for a species constellation consisting of perch (Perca fluviatilis) and roach (Rutilus rutilus) in a replicated whole lake experiment over 4 yr. Roach are preyed upon by large perch, but at the same time compete with small perch for zooplankton. Predictions regarding the effects of roach on perch performance and resource dynamics in the whole-lake experiment were based on results from previous pond and enclosure experiments carried out over short (months) time periods. Variables measured in the whole-lake experiment included both individual level parameters (diet and growth of perch) as well as population level parameters (mortality, population numbers and size structures of perch, abundance and biomass of zooplankton and benthic macroinvertebrates). The population size of perch ≥ 2 yr old decreased to less than 10% of the pre-treatment levels in treatment lakes after the introduction of roach and remained low over the whole study period. The mortality in perch one-year-old and older increased with size. Larger perch had a higher growth decrease than smaller perch, but also the individual growth rate of young-of-the-year (YOY) perch was lower in treatment lakes than in control lakes. YOY perch were almost excluded during the winter and spring following the roach introduction. The few perch of this year class that survived had the following years a higher growth than the corresponding year class in control lakes. This could be related to an increased availability of predator-sensitive macroinvertebrates in treatment lakes. Perch in treatment lakes fed to a larger extent on macroinvertebrates and less on pelagic zooplankton than perch in control lakes. As expected, zooplankton abundances decreased in treatment lakes the year following the roach introduction, but thereafter zooplankton abundances were higher in treatment lakes due to the absence of perch recruitment in these lakes. No incidence of perch predation on roach was recorded during the study period. We attribute this to the spatial scale dependent escape ability and habitat use of vulnerable size classes of roach. YOY perch had a stronger impact on between-year variation in zooplankton than YOY roach and this can be related to the higher foraging (handling) capacity of the former and the restricted habitat use of the latter. Individual level parameters (diet, growth) had a higher statistical power than population level parameters (abundance, biomass, mortality), and small-scale experiments successfully predicted a higher proportion (81%) of the individual level parameters. However, the lower success in predicting population level responses (38%) was directly connected to a failure to predict individual level parameters (large perch diet and growth). Our results suggest that the small spatial scale was the major limitation on the predictive ability of the small-scale experiments.