Modafinil is a wakeness-promoting drug, which is effective in the treatment of narcolepsy; its effects on learning processes are however little studied. Thus, the present study was aimed at determining the effects of an acute modafinil injection on a serial reversal discrimination task performed in a T-maze in mice. Independent groups of mice varying by the level of pretest training (either 1 or 4 days of training) were used. Mice were injected each day with a gum arabic solution before each session began. On the second or the fifth day of training, a single dose of modafinil was injected before testing. Modafinil at 64 mg/kg but not at 32 mg/kg dramatically improved performance as compared to controls in subjects being trained 4 days, but not in subjects being trained 1 day. This improvement of learning was due to the more rapid emergence of a win-stay strategy in modafinil-treated subjects as compare to controls. Thus, our data show that an acute modafinil injection enhances learning processes. (C) 2003 Elsevier Inc. All rights reserved.