We have studied the effect of modafinil and amphetamine, two waking drugs, on the sleep-wake cycle of Sprague-Dawley rat. Both modafinil (64 or 128 mg/kg) and amphetamine (2.5 or 5 mg/kg) cause a dose dependent increase in wakefulness. However, amphetamine wakefulness is followed by a paradoxical sleep rebound on the injection day, whereas modafinil does not produce this effect. In modafinil-treated rats, the sleep pattern on the post-injection day is similar to that of controls, while that of amphetamine-treated rats is modified.