In both humans and laboratory animals, the reports of cognitive effects following acute amphetamine (Amph) administration are mixed and depend, for example, on the timing of administration (e.g. before or after task acquisition) and/or on the memory model used. Besides its cognitive effects, Amph produces other important behavioural effects, including alterations in anxiety and general activity, which could modify the subject's internal state, thereby facilitating state-dependent learning. Importantly, state-dependency has been linked to drug dependence in humans. This study evaluates the role of state-dependent learning in Amph-induced memory deficits in mice submitted to a discriminative avoidance task. Mice were given Amph (3 mg/kg) before training and/or before testing in the plus-maze discriminative avoidance task, an animal model that concomitantly evaluates learning, memory, anxiety-like behaviour and general activity. Pre-training Amph administration did not affect the ability to learn the discriminative task, but rather induced anxiogenic-like effects and a marked retention deficit in the test session. This memory impairment was completely absent when animals received Amph before both the training and the test sessions. Amph-induced memory impairment of a discriminative avoidance task is state-dependent, such that a response acquired in the 'Amph state' cannot be recalled in the normal state. The involvement of anxiety alterations in this 'Amph state' is discussed.