The present study demonstrates a relationship between individual responses to environmental activation, such as novelty, and propensity to acquire amphetamine self-administration. Locomotor activity cumulated over 2 h of exposure to a circular corridor was a stable and novelty-dependent feature of behaviour in individual rats. The differences between subjects in this behaviour were maintained over two trials at 1 months intervals, but disappeared over 4 days when the animals were tested daily, i.e. when the environment was no longer novel. The subjects with the higher locomotor response to novelty (HR group) also showed a higher propensity to acquire amphetamine self-administration, while the subjects with the lower response to novelty (LR group) did not acquire self-administration over 7 days of testing. Differences in self-administration of HR animals could not be accounted for by differences in exploratory behaviour. Thus, HR animals did not show higher investigative responses in a hole exploration test. Animals with the higher locomotor response to novelty also showed a greater release of corticosterone in the same environment. Since dopaminergic (DA) neurons are activated by both amphetamine and novelty, it is possible that differences in the propensity to acquire amphetamine self-administration may be accounted for by differences in the activity of DA neurons.