Abstract Apparent rapid tolerance to ethanol for decrease in nerve conduction velocity, lasting up to one day but to seven days, was shown in HS mice following a single injection (i.p.) of 3.0 g EtOH/kg body wt. Relative conduction time (RCT-reciprocal of velocity) was studied in the caudal nerves of 60 mice. In Exp. 1 30 mice were tested twice, 7 days apart; these showed no significant change in RCT on re-test. In Exp. 2 30 mice tested twice, 1 day apart, showed a significantly smaller response to ethanol in the second test. This result suggests that ethanol tolerance in peripheral nerve conduction velocity may develop in these mice after a single ethanol dose. In addition, ethanol effects on two measures of CNS depression also suggest tolerance after one day and lasting to seven days. The basis for these apparent examples of tolerance to ethanol is not clear.