The effects of nicotine, when administered either acutely or chronically, at doses of 0.15, 0.3 or 0.6 mg/kg, on the release of glutamate and arginine in the rat nucleus accumbens have been studied in microdialysis experiments. Glutamate release significantly increased after acute nicotine injection, 0.3 mg/kg, which was accentuated if there was a priming regime of saline for the previous 27 days. This is possibly related to the rewarding effects of nicotine. Five hours after cessation of chronic oral nicotine administration, there were significant increases in glutamate content, which was possibly reflective of a withdrawal process. Significant decreases in nucleus accumbens arginine release were evident, between 1 and 2 h, after chronic nicotine administration. When nicotine was co-administered to rats during chronic ethanol intoxication, at either 0.15 mg/kg or 0.3 mg/kg doses, glutamate release did not increase during the first 12 h of withdrawal. However, a decrease in arginine microdialysate content was still observed with all nicotine doses. The nicotine-induced changes in glutamate and arginine release in nucleus accumbens highlights the complex neuropharmacological interactions evoked by this compound and also identified its possible modulating effect on glutamate release during the initial stages of chronic ethanol withdrawal.