R. V. McDonald and S. Siegel (see record 2004-10475-001) present convincing evidence that a small dose of morphine (5 mg/kg) may elicit withdrawal signs in rats previously injected on a number of occasions with a large dose of morphine (50 mg/kg), thus suggesting that intra-administration associations may be involved in drug withdrawal. This finding is important for basic and applied researchers studying drug reward mechanisms. Although R. V. McDonald and S. Siegel point out that the morphine conditional stimulus (CS) and unconditioned stimulus (US) making up the intra-administration association differ in onset and magnitude, the author of this comment argues that the CS and US may also differ in terms of pharmacologic activity.