John Huston may have regarded Wise Blood highly, but film studies has had comparatively little interest in it, favoring other, “classic” Huston films. In some ways, this is understandable. Wise Blood is an acquired taste: a low-budget, independently financed film with no stars that closely follows the Georgia author Flannery O'Connor's (1925–1964) bizarre, comic-horrific account of the southern orphan Hazel Motes's futile rebellion against his religious heritage. The characters are wholly unsympathetic, their interactions unpredictable and highly episodic, and the film, like O'Connor's novel, adopts a cool, ironic, and blackly humorous tone toward their truly outlandish antics.

Yet the more closely one examines the film, the more one is struck by how artfully it conveys O'Connor's highly symbolic, theologically imbued story. While adaptation studies has taken stock of and dismissed the notion of a film's “fidelity” to a source-text, Wise Blood is one adaptation where fidelity was the keynote principle of the filmmakers and the film itself. Equally compelling is how well its concerns coincide with those of many of Huston's other films – even though Huston himself did not write the film's screenplay. For the film features an uncanny conjunction of O'Connor's distinctive view of southern male identity gone awry with Huston's much-appreciated debunking of American masculine ethos.