The reinstatement of extinguished cocaine self‐administration behavior was studied in rats pretreated withN‐methyl‐d‐aspartate receptor antagonists. Rats were trained to self‐administer intravenous cocaine (0.32 mg/kg/infusion) during five consecutive daily sessions that were followed by five consecutive daily extinction sessions, during which cocaine was unavailable and cocaine‐associated cues (sound and light) were absent. Neither the competitiveN‐methyl‐d‐aspartate receptor antagonist d‐CPPene (0.3–3 mg/kg) nor the low‐affinityN‐methyl‐d‐aspartate receptor channel blocker memantine (1–10 mg/kg) reinstated extinguished responding. Priming injections of intravenous cocaine (Experiment 1), and exposures to cocaine‐associated stimuli (buzzer and light; Experiment 2) engendered responding on the reinforced lever in excess of that on the non‐reinforced lever. In Experiment 1, administration of d‐CPPene or memantine prior to the priming injection of cocaine eliminated the difference between reinforced‐lever and non‐reinforced‐lever response rates. For both d‐CPPene and memantine, however, this effect was largely due to increased responding upon the non‐reinforced lever rather than to decreased reinforced‐lever responding. In Experiment 2, d‐CPPene, but not memantine, abolished in a dose‐dependent manner the selective increase in reinforced‐lever over non‐reinforced‐lever responding that was induced by exposures to cocaine‐related stimuli. This effect of d‐CPPene was not due to increased non‐reinforced‐lever responding. These data help define the boundaries within whichN‐methyl‐d‐aspartate receptor antagonists can prevent reinstatement of cocaine‐seeking behavior (e.g. type of antagonist used and reinstatement procedure)