Why do states vary in their responses to the development of nuclear weapons capabilities by other states? Existing explanation of state level proliferation responses offer inadequate insight into the wide variation in responses that occurs across time and space. The literature on international relations, foreign policy analysis, and threat perception offers important insights, however, into the phenomenon. This dissertation argues that two structural factors – the degree of relational proliferation threat and the extent to which prioritizing anti-proliferation policies requires costly tradeoffs – are the primary drivers of proliferation response. The more threatening the state in question, and the lower the cost of taking action to prevent its acquisition of nuclear weapons capabilities, the stronger and more consistent will be a responder’s proliferation opposition. However, outcomes ultimately depend on how leading policymakers perceive these threats and tradeoffs, as well as the extent to which domestic and international scope conditions bound state behavior and manipulate cost tradeoffs. The two case studies explored in this dissertation are U.S. responses to the Indian and Israeli nuclear programs. In each case, the initial U.S. response was to oppose the acquisition of nuclear weapons capabilities. But this opposition diminished over time, resulting in accommodation of the reported acquisition of such capabilities by both states, a policy that continues today. This transition from opposition to accommodation is found to derive primarily from a combination of increasingly friendly relations and the high strategic cost tradeoffs of opposition, particularly as they were perceived by leading policymakers. At times, domestic and international scope conditions shaped U.S. responses in each case, but they did not fundamentally drive American preferences.