The local effect of nicotine on the extracellular levels of amino acids was examined in the striatum and frontal cortex of rats using microdialysis in vivo. The perfusion of 1 mM nicotine in Ringer's solution increased the extracellular levels of aspartic and glutamic acids by 40-50% in the striatum and had no effect on the levels of serine, glycine, glutamine, taurine or threonine. This effect of nicotine was dose- and Ca-dependent. At a 5 mM concentration, nicotine produced a more than 200% increase in the levels of aspartate, glutamate and taurine in the striatum; levels of glycine and threonine were also increased. Nicotine also increased the levels of these amino acids in the microdialysate from the frontal cortex. The effect of nicotine, tested in the striatum, was not influenced by mecamylamine or tetraethyl-ammonium chloride or haloperidol, but it was blocked by atropine. This indicated that muscarinic, cholinergic receptors participated in this effect of nicotine.