Although it is commonly believed that chronic alcohol abuse results in loss of neocortical neurons, this assumption has not been properly tested. We used new stereological techniques to make a precise and unbiased estimate of the total number of neurons in the neocortex of brains obtained at necropsy from 11 chronic alcoholic men and 11 control men. The groups were matched with respect to age and height. Total mean neocortical neuron numbers in the two groups did not differ (alcoholics 23.4 x 10(9), controls 23.2 x 10(9)). Estimation of macroscopic brain volumes showed significant reductions in alcoholics compared with controls of the volume/weight ratios of white matter (11%, p = 0.013) and of archicortex (30%, p = 0.028). The volume of the ventricles in the alcoholic group was enlarged by 26%, but this was not statistically significant. There was no difference in the volumes of the neocortices. Our study confirms that chronic alcoholics lose white matter, and this could provide the basis for their functional impairment. However, the results also suggest that the observed brain damage in the alcoholic group is potentially reversible since preserved nerve-cell bodies might allow lost or malfunctioning axons to re-established and restored to function after prolonged abstinence and/or treatment. By contrast, lost neocortical neurons cannot be replaced.