Two brothers, Charlie and Eli Sisters, are hired gunslingers out to track down and kill a prospector named Herman Kermit Warm. A frontier baron called the Commodore sends Charlie and Eli Sisters out to kill a thief; chemist-turned-prospector named Herman Kermit Warm. No reason is given and no questions are asked as the brothers travel from Oregon to San Francisco; eventually finding Warm in the Sierra foothills. An existentialist tale as much as a western, the Sisters Brothers discuss their relationship and their dreams along the way. Charlie Sisters, the eldest, is a selfish brute; a cold hearted killer with a mean streak, whereas brother Eli is a philosopher who wants to get out of the game. Along the way they run into a witch, who casts some unexplained spell on the pair after they stumble into her abandoned cabin. As Charlie goes out to find help, Eli see a bear attacking his horse and shoots it, but he's afraid to cross the witches charm placed over the door. When he eventually escapes the cabin through a window he discovers that his horse Tub has been wounded and blinded in one eye. The brothers trod on, coming across a dead Indian, a group of drunken whores, and then a gang of murderous fur trappers.
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The brothers are to meet Henry Morris, the Commodore's scout, in San Francisco, but discover instead that Morris and Warm have formed an allegiance and left for for Warm's gold claim outside of Sacramento. Morris' diary (left behind by Morris) details Warm's invention: a formula that detects hidden gold in the river. The brothers realize that the Commodore lied: Warm didn't steal anything, it is the Commodore who wants to steal from Warm so, after the brothers find Warm and Morris at the prospecting site (which leads to an initial gun battle), they decide to betray the Commodore and throw in with Warm and Morris and the new invention. They indeed find gold, but then Charlie makes a critical error during the process of dumping the chemicals into the water and both Morris and Warm end-up dead. The brothers then decided to steal Warm's formula for themselves then return to Oregon and kill the Commodore. They find him and get taken by him and then they travel to their mother's house as beaten men.
Best part of story, including ending:
This is a western in a modern vein, one where character plays as much a role as the mission, and Eli's narration is at times both perverse and darkly funny as he describes their plight; how he discovers dental hygiene; and ruminates on love with a whore. Charlie and Eli explore the human condition and destroy many of the clichés of the Old West.
Best scene in story:
When out on the range, Charlie makes a dinner of beans and pork and biscuits, but Eli eats only the beans and gives the rest to Tub.
Opinion about the main character:
Charlie has no real redeeming characteristics. His is mean and a drunkard who bullies his younger brother.