The nucleus basalis magnocellularis (NBM) is one element in the limbic cortical-ventral striatal circuitry that has been implicated in reinforcement processes. The present study examined the involvement of the cholinergic neurons of the NBM in mediating aspects of cocaine reinforcement. Lesions of the NBM were made by injecting 0.01 M AMPA into the subpallidal basal forebrain. Following 4 days' recovery, rats were implanted chronically with catheters in the jugular vein. In three separate experiments, rats were trained to acquire cocaine self-administration under a FR1 schedule of reinforcement at doses of 0.25, 0.083 and 0.028 mg/injection. A dose-effect function was also determined at the end of the acquisition experiments using five different doses of cocaine (0.009, 0.028, 0.083, 0.25, 0.50 mg/injection) and saline which were presented once daily in a Latin square design. There were no significant differences between groups in the acquisition of cocaine self-administration at any of the three doses studied (0.028, 0.083 and 0.25 mg/injection), although at the lowest dose, lesioned animals responded at greater levels on both active and inactive levers. However, a shift to the left in the cocaine dose-response function was observed revealing that the lesioned group self-administered significantly higher amounts of low doses of cocaine than control rats. These data suggest that the integrity of the NBM is not a critical determinant of the reinforcing effects of cocaine during the acquisition of self-administration of the drug, but that NBM-dependent cholinergic mechanisms may nevertheless interact with the neural substrates mediating the reinforcing properties of cocaine. The data are relevant to recent hypotheses of functional interactions between the dopaminergic system and the cholinergic NBM.