Spatial variation in disease risk in wild populations can depend both on environmental and genetic factors. Understanding the various contributions of each factor requires experimental manipulation of both the environment and genetic composition of populations under natural field conditions. We first examined natural patterns of oomycete composition and infection in the eggs of 13 populations of the spotted salamander Ambystoma maculatum. We then performed a fully factorial field transplant of the eggs of six populations to separate the contributions from population of origin and the environment on oomycete resistance in spotted salamanders. Among wild ponds, we found strong variation in oomycete infections in spotted salamander populations and differences in the composition of oomycete communities. In transplant experiments, salamander populations differed in their resistance to oomycete infections via a significant interaction between population of origin and environment. However, not all populations were locally adapted to local conditions. One population was significantly adapted to its home environment, and another one was significantly maladapted. These population effects could originate from differential adaptation of salamander populations to local oomycete communities or environmental conditions that mediate resistance, local adaptation and maladaptation of oomycetes to hosts, or from maternal transmission. Accounting for both environment and population of origin will often be necessary to understand disease dynamics in wild populations.