Samples of the cerebral cortex (left hemisphere, area 6) were collected at autopsy, between 4 and 6 h after death in order to avoid artifacts related to fixation delay, from 5 chronic alcoholic patients (in which well-defined alcoholic-malnutritional encephalopathies were excluded) and 16 controls; samples were immediately processed according to the rapid Golgi method. The curves representing the average density of dendritic spines on the apical dendrites of layer V pyramidal neurons as a function of the distance from the cell body were adjusted to a logarithmical model which was shown to be similar in controls and alcoholic groups. Significant reduced numbers of dendritic spines were observed; however, in the alcoholic patients when compared to age-matched controls (P less than 0.001; Kruskall-Wallis chi 2 test). These results demonstrate noxious effects of ethanol on cortical pyramidal neurons in human chronic alcoholism.