The effect of chronic ethanol treatment on long-term potentiation (LTP), a possible substrate for memory, was studied in rats using the in vitro hippocampal slice preparation. Rats were provided ad libitum access to an ethanol-containing or control liquid diet. One group of animals received the diet for a total period of 9 months before testing, while a second group received the diet for 7 months and was allowed a 2 month ethanol-free period before testing. LTP was induced in the CA1 region by orthodromic stimulation of the stratum radiatum with 4 stimulus trains of 200 pulses each at 25, 50, 100 and 200 Hz separated by 10 min intervals. The number of slices with potentiation greater than 15% was significantly smaller in the ethanol-fed animals both before and following the 2 month withdrawal period. However, the average percent increase in the amplitude of the population spike was significantly decreased in the ethanol-fed animals when tested before withdrawal but no significant difference was detected following the 2 month withdrawal period, suggesting some recovery. The possible mechanisms mediating the chronic ethanol-induced depression of LTP are discussed.