Animals treated with daily lidocaine (60 mg/kg, i.p.) develop progressive increases in pathological eating of nonnutritive substances, i.e. omniphagia. Bilateral amygdala lesions blocked the development of lidocaine-induced omniphagia. Following 32 daily injections of lidocaine, both lesioned and nonlesioned animals showed greater cocaine-induced hyperactivity than saline-pretreated controls. These data suggest cross-sensitization between the two local anesthetics lidocaine and cocaine, even though lidocaine does not possess the psychomotor stimulant effects of cocaine. Amygdala-lesioned animals showed greater cocaine-induced vertical rearing activity compared to controls. The lesion data suggest that the amygdala is differentially involved in the progressive behavioral sensitization to both chronic lidocaine and cocaine.