Rats were implanted with stimulating electrodes in the medial forebrain bundle-lateral hypothalamus (MFB-LH). Following recovery from surgery, they were placed in 3 groups prior to brain self-stimulation training. This consisted of one 15-min session on each of 5 consecutive days. Animals in the first group (controls) were placed in a conventional, single lever operant chamber without any additional manipulation. There were no priming stimuli, there was no experimenter intervention of any kind, and no exteroceptive cues in the chamber to indicate the availability or otherwise of the reinforcement. Animals in the second group (saline-injected) were treated similarly to the first group except that they were weighed and injected subcutaneously with saline (1 ml/kg) immediately before being placed in the chamber. Animals in a third group (D-amphetamine-injected) were weighed and administered D-amphetamine (0.5 mg/kg in saline) immediately before being placed in the chamber. The number of lever-presses made per 15-min session was recorded. In addition, the time taken to achieve a lever-pressing rate of 10 presses per min was recorded. There were no significant differences between groups in the number of presses per 15-min session. Animals administered D-amphetamine reached the rate of 10 presses per min significantly more rapidly than animals administered saline, but the latter did so significantly more rapidly than controls. These results demonstrated that the simple manipulation, and perhaps the mild stress, associated with a saline injection strongly affected the acquisition of a brain self-stimulation task.