Rats implanted with electrodes in the medial forebrain bundle-lateral hypothalamus were trained in a discrete trial procedure to make a differential response (right or left lever press) in the presence or absence of brain stimulation [intracranial self-stimulation (ICSS)]. When animals reached a high level of accuracy (95% correct) in the discrimination task, testing was begun. In the first experiment, we compared the effects of saline and 0.3 mg/kg d-amphetamine when the intertrial interval (ITI) was 1, 5, 10, and 15 s. In the second experiment, animals were tested either with saline, 0.3 mg/kg d-amphetamine, or 1, 3, or 10 mg/kg nomifensine and the ITI was held constant at 5 s. Increasing the ITI from 1-15 s did not produce a drug-induced change in the discriminative stimulus properties of ICSS, although it did produce changes in total numbers of lever presses and numbers of intertrial lever presses. In the second experiment, neither d-amphetamine nor nomifensine altered the discriminative stimulus properties of ICSS, but a dose-response increase occurred in the time to complete the test session and in total number of lever presses and in presses on the initiating lever. Under conditions known to increase extracellular dopamine (DA) levels in brain, both amphetamine and nomifensine produced large increases in locomotor activity, but neither drug produced changes in the detection threshold for ICSS. Results indicated that the internal cues produced by ICSS are different from those produced by these psychomotor stimulant drugs.