BACKGROUND Environmental context has been shown to influence responding under multiple schedules of food reinforcement and to modify the behavioral effects of drugs. However, no systematic study has been conducted under conditions of cocaine self-administration. The hypothesis was that changes in the magnitude of food reinforcement would affect cocaine-maintained response rates and influence the behavioral potency of a dopamine antagonist to decrease cocaine self-administration. OBJECTIVE A multiple schedule was used to evaluate the effects of changes in the magnitude of food reinforcement on the self-administration cocaine dose-response curve and on the behavioral potency of a dopamine receptor antagonist to decrease food- and cocaine-maintained responding. METHODS Rhesus monkeys (n=3) were trained to self-administer intravenous cocaine under a multiple fixed-interval (FI) 5-min schedule of food and cocaine presentation. Food (one or four pellets) was available in the first and third components and cocaine (saline, 0.01-0.3 mg/kg per injection) was available in the second and fourth components. After completion of cocaine dose-response curves, the effects of the dopamine D(2)/D(3) receptor antagonist 2,3-dimethoxy-N-(9-p-fluorobenzyl)-azabicyclo[3.3.1]nonan-3beta-yl benzamide (MABN) were examined. RESULTS Cocaine- and food-maintained responding varied as a function of dose and were characterized as inverted U-shaped functions; cocaine-maintained response rates were significantly influenced by the magnitude of food in the other component. The behavioral potency of MABN on food- and cocaine-maintained responding was not influenced by the magnitude of food reinforcement. CONCLUSIONS These results suggest that cocaine self-administration under a multiple schedule with food reinforcement is influenced by the environmental context. These schedule interactions, however, did not alter the behavioral effects of a dopamine D(2)/D(3) receptor antagonist.