Results/Conclusions In four of six experimental ponds, we observed a major die-off of salamander larvae. Salamander signs of illness and community-wide effects suggest that local pesticide use was the most likely cause of die-offs. Die-offs were associated with pond instability involving mass invertebrate die-offs and algal blooms, in addition to severe tiger salamander mortality. Pesticide application rates in fields adjacent to ponds where die-offs occurred were up to 63 times greater than those around stable ponds that did not experience such crashes. We found large differences in growth and survival of native versus hybrid salamanders at these sites, with natives doing worst when hybrids were present. This result implies an interaction between environmental stress and the presence of hybrids in determining fitness outcomes for the threatened native species. In stable sites, hybrid frequency also influenced native CTS performance. Overall, our results suggest that agricultural activities may promote the displacement of native genes by introduced counterparts. Large, fast-growing hybrids also had greater negative impacts on native frogs, propagating detrimental effects through pond communities. These results show how interactions between land use and genetics can dramatically impact community structure and introduced allele frequencies on a short timescale.