To gain a better insight into the alterations of brain function after chronic ethanol, we measured the release of various neurotransmitters from nerve terminals of cortex and hippocampus isolated from rats chronically fed with ethanol. The K+-evoked release of [3H]acetylcholine (ACh), [3H]dopamine (DA), [3H]glutamate (Glu) and [ 3H]noradrenaline (NA) was determined in superfused synaptosomes of brain cortex and hippocampus from rats exposed to the Lieber-DeCarli alcohol liquid diet for 5 weeks. In cortical synaptosomes, chronic ethanol administration did not affect the release of ACh and of DA, while significantly decreasing the release of Glu and NA. The endogenous levels of NA, DA and their metabolites were unchanged. In hippocampal synaptosomes the only effect of chronic alcohol was an increased release of Glu. It can be concluded that at presynaptic level chronic ethanol alters brain neurotransmitter systems selectively. Glutamatergic and noradrenergic nerve terminals from cortex are more vulnerable than those from hippocampus.