The aim of this paper is to discuss the relations between the American government and the American missionaries. The discussion is based on the relations between the missionaries of the American Board of Commissioners for Foreign Missions -the biggest Protestant missionary organization- and the American diplomats in the Ottoman Empire and Turkey in the Nineteenth and Twentieth centuries. It is a well known fact that missionary activities were never only religious activities. Missionaries looked after interests of their own countries. The American Protestant missionaries were not exceptional. They were the tools of the American interests in the Middle East. First of all the missionary institutions were American institutions. Therefore missionaries and diplomats collaborated. The American diplomats in Anatolia were there to protect the missionaries. The missionaries, on the other hand, provided information to the American consuls, embassy and the government. However, sometimes the missionaries claimed that the American diplomats did not protect them and the American interests in Anatolia, and criticized the diplomats. And the diplomats, on the other hand, thought that the missionaries were not representing the facts, and discredited them. When there was a disagreement between the diplomats and the missionaries, the latter did not hesitate to complain to the government, and put any kind of pressure on them since they had access to the media and the Capitol. The missionaries sometimes managed to discharge them, and sometimes had to forget their claims and follow the American policy determined in Washington DC. The relations of A.W.Terrell and Amiral Bristol with the American missionaries, and the positions of the American missionaries on the Lousanne Conference and Treaty will be highlighted. Apart from the relevant English and Turkish literature, correspondences and diaries of the missionaries and diplomats from the ABCFM and Library of Congress` archives will be used.