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Defender of English Dissenters and French revolutionaries

Although Priestley spent much of this time defending phlogiston theory from the "new chemists", most of what he published in Birmingham was theological. For example, in 1782, he published the fourth volume of his Institutes, An History of the Corruptions of Christianity, describing how he thought the teachings of the early Christian church had been "corrupted" or distorted. Schofield describes the work as "derivative, disorganized, wordy, and repetitive, detailed, exhaustive, and devastatingly argued". The text addresses issues ranging from the divinity of Christ to the proper form for the Lord's Supper. In 1786, Priestley published its provocatively titled sequel, An History of Early Opinions concerning Jesus Christ, compiled from Original Writers, proving that the Christian Church was at first Unitarian. Thomas Jefferson later wrote of the profound effect that these two books had on him: "I have read his Corruptions of Christianity, and Early Opinions of Jesus, over and over again; and I rest on them... as the basis of my own faith. These writings have never been answered." Although a few readers such as Jefferson and other Rational Dissenters approved of the work, many others reviewed it harshly because of its extreme theological positions, particularly its rejection of the Trinity.

In 1785, while Priestley was engaged in a pamphlet war over Corruptions, he also published The Importance and Extent of Free Enquiry, claiming that the Reformation had not really reformed the church. In words that would boil over into a national debate, he challenged his readers to enact change:

Let us not, therefore, be discouraged, though, for the present, we should see no great number of churches professedly unitarian.... We are, as it were, laying gunpowder, grain by grain, under the old building of error and superstition, which a single spark may hereafter inflame, so as to produce an instantaneous explosion; in consequence of which that edifice, the erection of which has been the work of ages, may be overturned in a moment, and so effectually as that the same foundation can never be built upon again....

Although discouraged by friends from using such inflammatory language, Priestley refused to back down from his opinions in print and he included it, forever branding himself as "Gunpowder Joe". After the publication of this seeming call for revolution in the midst of the French Revolution, pamphleteers stepped up their attacks on Priestley and he and his church were even threatened with legal action.

In 1787, 1789, and 1790, Dissenters again tried to repeal the Test and Corporation Acts. Although they might have succeeded initially, by 1790, with the fears of revolution looming in Parliament, few were swayed by appeals to equal rights. Political cartoons, one of the most effective and popular media of the time, skewered the Dissenters and Priestley. In Parliament, William Pitt and Edmund Burke argued against the repeal, a betrayal that angered Priestley and his friends, who had expected the two men's support. Priestley wrote a series of Letters to William Pitt and Letters to Burke.

Dissenters such as Priestley who supported the French Revolution came under increasing suspicion as scepticism regarding the revolution grew. In its propaganda against " radicals ", Pitt's administration used the "gunpowder" statement to argue that Priestley and other Dissenters wanted to overthrow the government. Burke, in his famous Reflections on the Revolution in France (1790), tied natural philosophers, and specifically Priestley, to the French Revolution, writing that radicals who supported science in Britain "considered man in their experiments no more than they do mice in an air pump". Burke also associated republican principles with alchemy and insubstantial air, mocking the scientific work done by both Priestley and French chemists. He made much in his later writings of the connections between "Gunpowder Joe", science, and Lavoisier—who was improving gunpowder for the French in their war against Britain. Paradoxically, a secular statesman, Burke, argued against science and maintained that religion should be the basis of civil society, whereas a Dissenting minister, Priestley, argued that religion could not provide the basis for civil society and should be restricted to one's private life.

Priestley also supported the campaign to abolish the British slave trade and published a sermon in 1788 in which he declared that nobody treated enslaved people "with so much cruelty as the English".