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The Valley Oil Company, owned by physician Doc Higgins, is the target of raids sabotaging drilling, and Doc cannot figure out who is behind the gang responsible. One afternoon, a raid results in the death of a worker, and Doc fires the foreman, Plummer, for letting the men drink on the job. The continual setbacks discourage financier John Travers, who is considering advising the local ranchers to withdraw their funds from the project, even though the railroad has promised to put a line through the town if a gusher is brought in. Plummer goes to town, where he confers with saloon owner Sam Daggett, the secret leader of the gang. Daggett has a second lease on the land that will go into effect if Doc's lease expires before he strikes oil, and he has hired a gang of outlaws, aided by Plummer, to sabotage Doc's work. Daggett is angry with Plummer for getting fired, but Plummer conspires with him to ensnare Ned Foster, another of Doc's men, into working for them. That evening, Daggett rigs a poker game so that Foster is losing heavily. Foster hides in another room when Doc enters the saloon to look for him, and Doc is thrown out by Daggett's thugs. Just then, "Stony" Brooke, "Tucson" Smith and "Lullaby" Joslin, friends known as The Three Mesquiteers, arrive. Doc had sent for the Mesquiteers in the hope that they could stop the gang, and the Mesquiteers start with the thugs in the saloon. While the brawl is going on, Doc's bag is tossed into the room where Foster is hiding, and Foster inadvertantly mixes up the spilled medications as he replaces them in their bottles. One bottle remains on the floor and is picked up by Daggett. After the sheriff restores order, Doc tends to Plummer, who received a head wound. Plummer dies soon after though, and the coroner determines that Doc gave him the wrong pills and poisoned him. Doc is mystified but is cleared of wrongdoing, and the Mesquiteers settle into town. Blackmailing Foster with the leftover bottle and the gambling debts, Daggett forces him to aid the gang in sabotaging the oil well. Foster enlists two other men, Todd and Jensen, who throw rocks down the well late one night. Their act is witnessed by Travers, however, who has just had an argument with Doc, whom he told he would no longer support. Foster follows Travers back to his home and there switches his medication with more of the poison in Doc's bag. After Travers dies, his daughter Jean accuses Doc of killing him because of their argument. The Mesquiteers, believing in Doc's innocence, rescue him from the sheriff and search for the real killers. They find Foster's IOU's and the poison bottle in Daggett's office, and later, at the well, use some knockout drops to elicit confessions from both Foster and Daggett. Jean and a posse arrive at the well in time to round up the rest of the gang, and after a weary Lullaby sits on a dynamite plunger, the oil well is brought in.