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Institutional fit is operationalized by transferring transaction costs economics (TCE) to the analysis of instances of social-ecological interdependence. We carefully spell out the differences with conventional TCE and outline analytical steps based on discriminating alignment that enable a TCE analysis of environmental governance of “nature-related transactions”. We illustrate the approach through the example of wildlife management in Germany. Here we find hierarchical governance (a prohibition) of killing of wolves embedded into a polycentric hybrid monitoring arrangement. In applying TCE to nature-related transactions, we argue that characteristics of nature-related transactions can be subsumed under the core categories of jointness, uncertainty, asset specificity, frequency, rivalry, excludability and social-relational distance. Benefits of this approach include its generating a narrow list of descriptors of instances of biophysically mediated interdependence related to one evaluation criterion: cost-effectiveness. The TCE of nature-related transactions thus identifies sets of stylized contextual factors and aspects related to the governance of hazards of ex-post opportunistic behavior that cut across scales. They can be used as composite descriptors that facilitate analysis of complex multi-scalar arrangements of natural resource governance. We propose the concept of ‘governance challenge’, derived from TCE, as being useful for building research on environmental governance.