The possibility that the atypical neuroleptic olanzapine can antagonize the ability of cocaine to produce both conditioned place preference and self-administration in rats was investigated. Pre-treatment with olanzapine (3.0, 4.5 mg/kg, but not 1.5 mg/kg) significantly attenuated conditioned place preference produced by cocaine (10 mg/kg). However, the higher dose of olanzapine administered alone resulted in conditioned place aversion. Pre-treatment with olanzapine also produced a dose-dependent decrease in cocaine self-administration (0.33 mg/infusion) under a fixed-ratio 2 schedule of reinforcement. Olanzapine produced a similar dose-responsive attenuation in operant responding for food (fixed-ratio 10) suggesting that olanzapine produces a nonspecific decrease in operant behavior. Pre-treatment with 4.5 mg/kg olanzapine significantly attenuated cocaine-induced hyperactivity, whereas lower olanzapine doses had little effect upon cocaine-induced hyperactivity. These results suggest that pre-treatment with olanzapine is capable of blocking the reinforcing effects of cocaine and illustrates the value of using multiple tests of reinforcement when evaluating the pharmacological effects of newer psychotherapeutic agents.