Abstract This article reads Saul Bellow’s Humboldt’s Gift (1975)—a novel best known for its fictionalized portrait of the writer Delmore Schwartz—according to a conceptual sympathy between friendship and the novel. Though such a twinning can illuminate Bellow’s career as a whole, I argue here that Humboldt’s Gift represented his most compelling and complex attempt to reckon with opposition as an artistic problem (and opportunity). In 1962, Bellow published an essay talking up the importance of managing ‘opposites’ within a novel and, in his novels of this period, he alludes to an aphorism of William Blake’s: ‘Opposition is true friendship’. This statement, to begin with, fairly encapsulates the volatile relationship between the central characters of Charles Citrine and Von Humboldt Fleischer, but in this article I also interrogate the manifold ways in which an understanding of friendship as oppositional can illuminate mid-century theorizing about the novel as being fundamentally structured by oppositions. More idiosyncratically, Bellow recruits these sympathetic conceptions of friendship and the novel in pursuit of a quasi-gnostical synthesis whereby two exceptional friends might escape the indignities and mysteries of material existence. Elements such as the compositional record of Humboldt’s Gift, the influence of Blake’s Romantic ‘Contraries’, and Charles Citrine’s embarrassed enthusiasm for the ‘anthroposophy’ of Rudolf Steiner demonstrate a mutualistic intimacy between friendship and the novel. Friendship, that is, enlivens the novel with its varieties, flexibilities, and bantering confrontations; the novel, in turn, offers an indispensable forum for scrutinizing the duties and demands of friendship.