In his presidential address to the Belfast meeting of the British Association for the Advancement of Science in 1874, John Tyndall launched what David Livingstone has called a ‘frontal assault on teleology and Christian theism’. Using Tyndall's intervention as a starting point, this paper seeks to understand the attitudes of Presbyterians in the north of Ireland to science in the first three-quarters of the nineteenth century. The first section outlines some background, including the attitude of Presbyterians to science in the eighteenth century, the development of educational facilities in Ireland for the training of Presbyterian ministers, and the specific cultural and political circumstances in Ireland that influenced Presbyterian responses to science more generally. The next two sections examine two specific applications by Irish Presbyterians of the term ‘science’: first, the emergence of a distinctive Presbyterian theology of nature and the application of inductive scientific methodology to the study of theology, and second, the Presbyterian conviction that mind had ascendancy over matter which underpinned their commitment to the development of a science of the mind. The final two sections examine, in turn, the relationship between science and an eschatological reading of the signs of the times, and attitudes to Darwinian evolution in the fifteen years between the publication of The Origin of Species in 1859 and Tyndall's speech in 1874.