A computerized motor activity monitoring system was used to investigate the development and time dependence of sensitization to repeated exposure of amphetamine. Male Sprague-Dawley rats were acclimated for 7 days to light/dark cycle (0700 h:1900 h) in the testing room, and were then housed in the test cages for 16 days of continuous recording. The locomotor responses to s.c. administration of amphetamine (0.3, 0.6, or 1.2 mg/kg) were compared before and after five daily injections of 0.6 mg/kg of amphetamine. Different groups of rats were administered drug at either 0800 h, 1400 h, 2000 h, or 0200 h. The locomotor indices studied were total distance and vertical activity. Sensitization was more pronounced for total distance (i.e., forward ambulation) than for vertical activity (i.e., rearing), and its expression was dependent on the challenge dose. Sensitization was also time-dependent, with the strongest sensitized response occurring during the middle of the dark cycle (0200 h). Repeated administration of amphetamine (0.6 mg/kg) did not cause post-stimulant depression as has been seen at higher doses.