The effect of chronic (3-4 weeks), heavy ethanol exposure on neuronal vacuolation in rat peripheral nervous system was studied in male Wistar rats. The rats were force-fed with 25% ethanol 3 times a day, which resulted in blood ethanol levels of 53.1 +/- 18.8 mmol/l, i.e., marked intoxication. In the superior cervical ganglia (SCG), the ethanol exposure increased the proportion of vacuolated neurons c. 13-fold (0.2 +/- 0.0% in the control ganglia, 2.7 +/- 0.6% in the EtOH-ganglia, P < 0.001). A considerable population of vacuolated neurons (VN) was seen in the sensory inferior vagal (nodose) ganglia, and occasional neurons with large cytoplasmic vacuoles in the sensory dorsal root ganglia (DRG) of the EtOH-rats. In the hypogastric ganglia, where VN are regularly found in the adult rat, ethanol exposure did not affect the amount or the appearance of the vacuolated neurons. The number of VN in the SCG decreased significantly between 2 days and 1 week after cessation of the exposure, but did not return to control level by 1 month after ethanol withdrawal. In electron microscopy, most of the vacuolated SCG neurons showed normal ultrastructure, apart from the large cytoplasmic vacuoles. Some vacuolated neurons, however, showed neuropathologic changes, e.g., dilated endoplasmic reticulum, mitochondrial alterations and increased numbers of myelin figures. These degenerative changes were more frequent in the vacuolated DRG neurons than in the sympathetic ones. The occurrence of VN in rat peripheral ganglia may represent a reaction to increased stimulation during prolonged ethanol exposure and, especially, during repeated phases of ethanol withdrawal.