The infection assays showed a significant evolutionary response of hosts to epidemics in six of seven lake populations. In three lakes (Island, Midland, and Scott Lakes), host populations became significantly more resistant during epidemics (Fig. 1). However, in three other populations (Canvasback, Downing, and Hale Lakes), hosts became significantly more susceptible to infection. The hosts in the seventh lake, Beaver Dam, did not show a significant change in susceptibility but trended toward increased resistance. As anticipated by theory (SOM), these evolutionary trajectories correlated with ecologically driven variation in epidemic size. Among the six lake populations showing a significant evolutionary response, change in mean susceptibility correlated strongly with epidemic size (Pearson correlation: r= 0.86, P= 0.030, n= 6; Fig. 2A). Further, in those six lakes, epidemics were larger at lower predation intensity (larger size of hosts; Pearson correlation: r= 0.86, P= 0.029, n= 6; Fig. 2B) and where total nitrogen was higher (Pearson correlation: r= 0.83, P= 0.040, n= 6; Fig. 2C); the trend was similarly directed, but not significant, for total phosphorus (Pearson correlation: r= 0.50, P= 0.3, n= 6; Fig. 2D). Overall, hosts became more susceptible to the yeast in lower productivity lakes with higher vertebrate predation but evolved toward decreased susceptibility in more productive lakes with lower vertebrate predation (Fig. 2, E and F; t tests for differences between two groups; results for body size, t4= 3.19 and P= 0.033; nitrogen, t4= 3.18 and P= 0.034; phosphorus, t4= 0.88 and P= 0.43). Thus, ecological gradients, through their effects on epidemic size, influenced evolutionary outcomes of hosts during outbreaks of a virulent parasite. These qualitative predictions also arose from a general, trait-based epidemiological model built for similar epidemiology and parameterized for our particular system (SOM). These results show that hosts can evolve enhanced susceptibility to their virulent parasites during epidemics [also see (27) for a similar but unreplicated occurrence]. A combination of observations, experiments, and modeling all suggest causation for this initially counterintuitive finding. When ecological factors promote large epidemics, hosts should evolve to become more resistant to infection. However, resistancefecundity trade-offs can prompt host populations to evolve increased susceptibility when ecology constrains epidemic size. Overall, we demonstrated that ecological context influences epidemic size, which, in turn, determines evolutionary responses of hosts to epidemics. This suggests that alteration of predation pressure on hosts and productivity of ecosystems may influence the ecology and evolution of host-parasite interactions.